Researcher Profile - Yukio Sasaki

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写真a

Yukio Sasaki

Organization

Graduate School of Medical Life Science Department of Medical Life Science Associate Professor
School of Science Department of Science

Homepage

http://en.sasakilab.org

Profile

Neuroscience researcher. In 1993, I got PhD degree from Kobe University in research on protein kinase C. After joining a pharmaceutical company, I engaged in the development of an antagonist for vasoconstrictor endothelin. After studying the axon guidance factor semaphorin at Yokohama City University School of Pharmacology, I studied abroad in the United States and engaged in research on RNA binding protein. After returning to Japan, I am currently studying the relationship between RNA binding protein and neural circuit formation.

External link

Degree

Ph.D. ( Kobe University )

Research Interests

神経生物学
翻訳調節
神経回路網
ラベンダスチンA
神経発生
神経ガイダンス
横浜市
軸索輸送
4血管閉塞脳虚血
脳虚血上流因子内因性ドーパ
弧束核
Nogo
PTPase
チロシンホスファターゼ
神経細胞死因子ドーパ
細胞内情報伝達
シナプス
成長円錐
Synapse
Growth cone
セマフォリン
Synaptogenesis
Fragile X syndrome
軸策輸送
Local translation
Fyn
チロシンリン酸化
神経細胞死
チロシンキナーゼ
プレキシン
マイクロRNA
Cdk5
コラプシン
軸索ガイダンス
反発因子

Research Areas

Life Science / Cell biology
Life Science / Medical biochemistry
Life Science / Pharmacology
Life Science / Neuroscience-general
Life Science / Molecular biology

Research History

Yokohama City University Graduate School of Medical Life Scicence Functional Structure Laboratory, Division of Functional Structure Associate Professor

2013.4

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Yokohama City University Graduate School of Medicine Department of Molecular Neuroscience and Neurobiology Contract Associate Professor

2009.9 - 2013.4

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Emory University School of Medicine Department of Cell Biology Instractor

2005.8 - 2009.8

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Albert Einstein College of Medicine Department of Neuroscience Research associate

2002.9 - 2005.7

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Yokohama City University School of Medicine Department of Pharmacology Lecturer

2001.1 - 2002.8

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Yokohama City University School of Medicine Department of Pharmacology Instractor

1997.4 - 2001.1

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Ciba-Geigy Japan Limited Research scientist

1993.4 - 1997.3

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Papers

Predicting condensate formation of protein and RNA under various environmental conditions. Reviewed International journal

Ka Yin Chin, Shoichi Ishida, Yukio Sasaki, Kei Terayama

BMC bioinformatics 25 ( 1 ) 143 - 143 2024.4

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BACKGROUND: Liquid-liquid phase separation (LLPS) by biomolecules plays a central role in various biological phenomena and has garnered significant attention. The behavior of LLPS is strongly influenced by the characteristics of RNAs and environmental factors such as pH and temperature, as well as the properties of proteins. Recently, several databases recording LLPS-related biomolecules have been established, and prediction models of LLPS-related phenomena have been explored using these databases. However, a prediction model that concurrently considers proteins, RNAs, and experimental conditions has not been developed due to the limited information available from individual experiments in public databases. RESULTS: To address this challenge, we have constructed a new dataset, RNAPSEC, which serves each experiment as a data point. This dataset was accomplished by manually collecting data from public literature. Utilizing RNAPSEC, we developed two prediction models that consider a protein, RNA, and experimental conditions. The first model can predict the LLPS behavior of a protein and RNA under given experimental conditions. The second model can predict the required conditions for a given protein and RNA to undergo LLPS. CONCLUSIONS: RNAPSEC and these prediction models are expected to accelerate our understanding of the roles of proteins, RNAs, and environmental factors in LLPS.

DOI： 10.1186/s12859-024-05764-z

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Novel presynaptic assay system revealed that metformin ameliorates exaggerated synaptic release and Munc18-1 accumulation in presynapses of neurons from Fragile X syndrome mouse model. Reviewed International journal

Renoma Takeda, Rie Ishii, Shumaia Parvin, Aki Shiozawa, Terukazu Nogi, Yukio Sasaki

Neuroscience letters 810 137317 - 137317 2023.6

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Fragile X syndrome (FXS) is a developmental disorder characterized by intellectual disability and autistic-like behaviors. These symptoms are supposed to result from dysregulated translation in pre- and postsynapses, resulting in aberrant synaptic plasticity. Although most drug development research on FXS has focused on aberrant postsynaptic functions by excess translation in postsynapses, the effect of drug candidates on FXS in presynaptic release is largely unclear. In this report, we developed a novel assay system using neuron ball culture with beads to induce presynapse formation, allowing for the analysis of presynaptic phenotypes, including presynaptic release. Metformin, which is shown to rescue core phenotypes in FXS mouse model by normalizing dysregulated translation, ameliorated the exaggerated presynaptic release of neurons of FXS model mouse using this assay system. Furthermore, metformin suppressed the excess accumulation of the active zone protein Munc18-1, which is supposed to be locally translated in presynapses. These results suggest that metformin rescues both postsynaptic and presynaptic phenotypes by inhibiting excess translation in FXS neurons.

DOI： 10.1016/j.neulet.2023.137317

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Identification of FMRP target mRNAs in the developmental brain: FMRP might coordinate Ras/MAPK, Wnt/β-catenin, and mTOR signaling during corticogenesis. Reviewed International journal

Cristine R Casingal, Takako Kikkawa, Hitoshi Inada, Yukio Sasaki, Noriko Osumi

Molecular brain 13 ( 1 ) 167 - 167 2020.12

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Corticogenesis is one of the most critical and complicated processes during embryonic brain development. Any slight impairment in corticogenesis could cause neurodevelopmental disorders such as Fragile X syndrome (FXS), of which symptoms contain intellectual disability (ID) and autism spectrum disorder (ASD). Fragile X mental retardation protein (FMRP), an RNA-binding protein responsible for FXS, shows strong expression in neural stem/precursor cells (NPCs) during corticogenesis, although its function during brain development remains largely unknown. In this study, we attempted to identify the FMRP target mRNAs in the cortical primordium using RNA immunoprecipitation sequencing analysis in the mouse embryonic brain. We identified 865 candidate genes as targets of FMRP involving 126 and 118 genes overlapped with ID and ASD-associated genes, respectively. These overlapped genes were enriched with those related to chromatin/chromosome organization and histone modifications, suggesting the involvement of FMRP in epigenetic regulation. We further identified a common set of 17 FMRP "core" target genes involved in neurogenesis/FXS/ID/ASD, containing factors associated with Ras/mitogen-activated protein kinase, Wnt/β-catenin, and mammalian target of rapamycin (mTOR) pathways. We indeed showed overactivation of mTOR signaling via an increase in mTOR phosphorylation in the Fmr1 knockout (Fmr1 KO) neocortex. Our results provide further insight into the critical roles of FMRP in the developing brain, where dysfunction of FMRP may influence the regulation of its mRNA targets affecting signaling pathways and epigenetic modifications.

DOI： 10.1186/s13041-020-00706-1

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Local Translation in Growth Cones and Presynapses, Two Axonal Compartments for Local Neuronal Functions. Reviewed International journal

Yukio Sasaki

Biomolecules 10 ( 5 ) 2020.4

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During neural development, growth cones, very motile compartments of tips of axons, lead axonal extension to the correct targets. Subsequently, presynapses, another axonal compartment with vigorous trafficking of synaptic vesicles, emerge to form functional synapses with postsynapses. In response to extracellular stimuli, the immediate supply of proteins by local translation within these two axonal compartments far from cell bodies confers high motility of growth cones and active vesicle trafficking in presynapses. Although local translation in growth cones and presynapses occurs at a very low level compared with cell bodies and even dendrites, recent progress in omics and visualization techniques with subcellular fractionation of these compartments has revealed the actual situation of local translation within these two axonal compartments. Here, the increasing evidence for local protein synthesis in growth cones and presynapses for axonal and synaptic functions has been reviewed. Furthermore, the mechanisms regulating local translation in these two compartments and pathophysiological conditions caused by dysregulated local translation are highlighted.

DOI： 10.3390/biom10050668

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Semaphorin-3A Promotes Degradation of Fragile X Mental Retardation Protein in Growth Cones via the Ubiquitin-Proteasome Pathway. Reviewed International journal

Masaru Takabatake, Yoshio Goshima, Yukio Sasaki

Frontiers in neural circuits 14 5 - 5 2020

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Fragile X mental retardation protein (FMRP) is an RNA-binding protein that regulates local translation in dendrites and spines for synaptic plasticity. In axons, FMRP is implicated in axonal extension and axon guidance. We previously demonstrated the involvement of FMRP in growth cone collapse via a translation-dependent response to Semaphorin-3A (Sema3A), a repulsive axon guidance factor. In the case of attractive axon guidance factors, RNA-binding proteins such as zipcode binding protein 1 (ZBP1) accumulate towards the stimulated side of growth cones for local translation. However, it remains unclear how Sema3A effects FMRP localization in growth cones. Here, we show that levels of FMRP in growth cones of hippocampal neurons decreased after Sema3A stimulation. This decrease in FMRP was suppressed by the ubiquitin-activating enzyme E1 enzyme inhibitor PYR-41 and proteasome inhibitor MG132, suggesting that the ubiquitin-proteasome pathway is involved in Sema3A-induced FMRP degradation in growth cones. Moreover, the E1 enzyme or proteasome inhibitor suppressed Sema3A-induced increases in microtubule-associated protein 1B (MAP1B) in growth cones, suggesting that the ubiquitin-proteasome pathway promotes local translation of MAP1B, whose translation is mediated by FMRP. These inhibitors also blocked the Sema3A-induced growth cone collapse. Collectively, our results suggest that Sema3A promotes degradation of FMRP in growth cones through the ubiquitin-proteasome pathway, leading to growth cone collapse via local translation of MAP1B. These findings reveal a new mechanism of axon guidance regulation: degradation of the translational suppressor FMRP via the ubiquitin-proteasome pathway.

DOI： 10.3389/fncir.2020.00005

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Fragile X mental retardation protein regulates accumulation of the active zone protein Munc18-1 in presynapses via local translation in axons during synaptogenesis Reviewed International journal

Shumaia Parvin, Renoma Takeda, Yu Sugiura, Makiko Neyazaki, Terukazu Nogi, Yukio Sasaki

Neuroscience Research 146 36 - 47 2019.9

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Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier {BV}

Fragile X mental retardation protein (FMRP), a causative gene (FMR1) product of Fragile X syndrome (FXS), is an RNA-binding protein to regulate local protein synthesis in dendrites for postsynaptic functions. However, involvement of FMRP in local protein synthesis in axons for presynaptic functions remains unclear. Here we investigated role of FMRP in local translation of the active zone protein Munc18-1 during presynapse formation. We found that leucine-rich repeat transmembrane neuronal 2 (LRRTM2)-conjugated beads, which promotes synchronized presynapse formation, induced simultaneous accumulation of FMRP and Munc18-1 in presynapses of axons of mouse cortical neurons in neuronal cell aggregate culture. The LRRTM2-induced accumulation of Munc18-1 in presynapses was observed in axons protein-synthesis-dependently, even physically separated from cell bodies. The accumulation of Munc18-1 was enhanced in Fmr1-knockout (KO) axons as compared to wild type (WT), suggesting FMRP-regulated suppression for local translation of Munc18-1 in axons during presynapse formation. Using naturally formed synapses of dissociated culture, structured illumination microscope revealed that accumulation of Munc18-1 puncta in Fmr1-KO neurons increased significantly at 19 days in vitro, as compared to WT. Our findings lead the possibility that excessive accumulation of Munc18-1 in presynapses at early stage of synaptic development in Fmr1-KO neurons may have a critical role in impaired presynaptic functions in FXS.

DOI： 10.1016/j.neures.2018.09.013

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Presynapse Formation Assay Using Presynapse Organizer Beads and "Neuron Ball" Culture. Reviewed

Parvin S, Takeda R, Sasaki Y

Journal of visualized experiments : JoVE ( 150 ) 2019.8

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DOI： 10.3791/59893

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Regulation of dendritic development by semaphorin 3A through novel intracellular remote signaling Reviewed

Yoshio Goshima, Naoya Yamashita, Fumio Nakamura, Yukio Sasaki

CELL ADHESION & MIGRATION 10 ( 6 ) 627 - 640 2016

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DOI： 10.1080/19336918.2016.1210758

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Other Link： http://orcid.org/0000-0001-6143-7001
Plexin-A4-dependent retrograde semaphorin 3A signalling regulates the dendritic localization of GluA2-containing AMPA receptors Reviewed

Naoya Yamashita, Hiroshi Usui, Fumio Nakamura, Sandy Chen, Yukio Sasaki, Tomonobu Hida, Fumikazu Suto, Masahiko Taniguchi, Kohtaro Takei, Yoshio Goshima

NATURE COMMUNICATIONS 5 3424 2014.3

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DOI： 10.1038/ncomms4424

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Identification of Axon-Enriched MicroRNAs Localized to Growth Cones of Cortical Neurons Reviewed

Yukio Sasaki, Christina Gross, Lei Xing, Yoshio Goshima, Gary J. Bassell

DEVELOPMENTAL NEUROBIOLOGY 74 ( 3 ) 397 - 406 2014.3

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DOI： 10.1002/dneu.22113

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Regulation of neurite outgrowth mediated by localized phosphorylation of protein translational factor eEF2 in growth cones Reviewed

Masumi Iketani, Akira Iizuka, Kumiko Sengoku, Yuji Kurihara, Fumio Nakamura, Yukio Sasaki, Yasufumi Sato, Masayuki Yamane, Masayuki Matsushita, Angus C. Nairn, Ken Takamatsu, Yoshio Goshima, Kohtaro Takei

DEVELOPMENTAL NEUROBIOLOGY 73 ( 3 ) 230 - 246 2013.3

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DOI： 10.1002/dneu.22058

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Class 3 semaphorins as a therapeutic target Reviewed

Yoshio Goshima, Yukio Sasaki, Naoya Yamashita, Fumio Nakamura

EXPERT OPINION ON THERAPEUTIC TARGETS 16 ( 9 ) 933 - 944 2012.9

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DOI： 10.1517/14728222.2012.710201

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GSK3 beta/Axin-1/beta-Catenin Complex Is Involved in Semaphorin3A Signaling Reviewed

Tomonobu Hida, Naoya Yamashita, Hiroshi Usui, Fumio Nakamura, Yukio Sasaki, Akira Kikuchi, Yoshio Goshima

JOURNAL OF NEUROSCIENCE 32 ( 35 ) 11905 - 11918 2012.8

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DOI： 10.1523/JNEUROSCI.6139-11.2012

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Regulation of chemotropic guidance of nerve growth cones by microRNA Reviewed

Liang Han, Zhexing Wen, Rachel C. Lynn, Marie-Laure Baudet, Christine E. Holt, Yukio Sasaki, Gary J. Bassell, James Q. Zheng

MOLECULAR BRAIN 4 ( 1 ) 40 2011.11

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DOI： 10.1186/1756-6606-4-40

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CRMP5 (Collapsin Response Mediator Protein 5) Regulates Dendritic Development and Synaptic Plasticity in the Cerebellar Purkinje Cells Reviewed

Naoya Yamashita, Bedrich Mosinger, Arpita Roy, Mari Miyazaki, Kozue Ugajin, Fumio Nakamura, Yukio Sasaki, Kazuhiko Yamaguchi, Pappachan Kolattukudy, Yoshio Goshima

JOURNAL OF NEUROSCIENCE 31 ( 5 ) 1773 - 1779 2011.2

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DOI： 10.1523/JNEUROSCI.5337-10.2011

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Phosphorylation of Zipcode Binding Protein 1 Is Required for Brain-Derived Neurotrophic Factor Signaling of Local beta-Actin Synthesis and Growth Cone Turning Reviewed

Yukio Sasaki, Kristy Welshhans, Zhexing Wen, Jiaqi Yao, Mei Xu, Yoshio Goshima, James Q. Zheng, Gary J. Bassell

JOURNAL OF NEUROSCIENCE 30 ( 28 ) 9349 - 9358 2010.7

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DOI： 10.1523/JNEUROSCI.0499-10.2010

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Fragile X mental retardation protein is involved in protein synthesis-dependent collapse of growth cones induced by Semaphorin-3A Reviewed

Chanxia Li, Gary Bassell, Yukio Sasaki

JOURNAL OF PHARMACOLOGICAL SCIENCES 112 241P - 241P 2010

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Language：English Publisher：JAPANESE PHARMACOLOGICAL SOC

Li C, Bassell GJ, Sasaki Y, Frontiers in neural circuits, 2009, vol. 3, pp. 11, 2009

DOI： 10.3389/neuro.04.011.2009

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Semaphorin3A Signaling Mediated by Fyn-dependent Tyrosine Phosphorylation of Collapsin Response Mediator Protein 2 at Tyrosine 32 Reviewed

Yutaka Uchida, Toshio Ohshima, Naoya Yamashita, Miyuki Ogawara, Yukio Sasaki, Fumio Nakamura, Yoshio Goshima

JOURNAL OF BIOLOGICAL CHEMISTRY 284 ( 40 ) 27393 - 27401 2009.10

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DOI： 10.1074/jbc.M109.000240

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Fragile X mental retardation protein is involved in protein synthesis-dependent collapse of growth cones induced by Semaphorin-3A Reviewed

Chanxia Li, Gary J. Bassell, Yukio Sasaki

FRONTIERS IN NEURAL CIRCUITS 3 2009.9

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Fragile X syndrome, the most frequent form of familial mental retardation, is caused by mutation of the Fmr1 gene. Fmr1 encodes the fragile X mental retardation protein (FMRP), an mRNA binding protein regulating local, postsynaptic mRNA translation along dendrites necessary for long-term synaptic plasticity. However, recent studies on FMRP localization in axons and growth cones suggest a possible function in the regulation of local protein synthesis needed for axon guidance. Here, we have demonstrated that FMRP is involved in axonal and growth cone responses induced by the axon guidance factor, Semaphorin-3A (Sema3A). In cultured hippocampal neurons from wild type mice, Sema3A-induced growth cone collapse was protein synthesis-dependent. In contrast, Sema3A-induced growth cone collapse was attenuated in Fmr1 knock-out (KO) neurons and insensitive to protein synthesis inhibitors, suggesting that FMRP is involved in protein synthesis-dependent growth cone collapse. Sema3A increased phosphorylation of eukaryotic initiation factor 4E (eIF4E), an indicator of local translation, in distal axons and growth cones of wild type, but not Fmr1 KO neurons. Furthermore, Sema3A rapidly induced a protein synthesis-dependent increase in levels of microtubule associated protein 1B (MAP1B) in distal axons of wild type neurons, but this response was attenuated in Fmr1 KO neurons. These results suggest a possible role of FMRP to regulate local translation and axonal protein localization in response to Sema3A. This study reveals a new link between FMRP and semaphorin signaling in vitro, and raises the possibility that FMRP may have a critical role in semaphorin signaling in axon guidance during brain development.

DOI： 10.3389/neuro.04.011.2009

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Single molecule-sensitive probes for imaging RNA in live cells Reviewed

Philip J. Santangelo, Aaron W. Lifland, Paul Curt, Yukio Sasaki, Gary J. Bassell, Michael E. Lindquist, James E. Crowe

NATURE METHODS 6 ( 5 ) 347 - U46 2009.5

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DOI： 10.1038/NMETH.1316

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CRMP family protein: Novel targets for Cdk5 that regulates axon guidance, synapse maturation, and cell migration Reviewed

Yoshio Goshima, Yukio Sasaki, Yutaka Uchida, Naoya Yamashita, Fumio Nakamura

Cyclin Dependent Kinase 5 (Cdk5) 9 - 24 2008

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Language：English Publishing type：Part of collection (book) Publisher：Springer US

DOI： 10.1007/978-0-387-78887-6_2

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Extracellular stimuli specifically regulate localized levels of individual neuronal mRNAs Reviewed

Dianna E. Willis, Erna A. van Niekerk, Yukio Sasaki, Mariano Mesngon, Tanuia I. Merianda, Gervan G. Williams, Marvin Kendall, Deanna S. Smith, Gary J. Bassell, Jeffery L. Twiss

JOURNAL OF CELL BIOLOGY 178 ( 6 ) 965 - 980 2007.9

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DOI： 10.1083/jcb.200703209

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An essential role for beta-actin mRNA localization and translation in Ca2+-dependent growth cone guidance Reviewed

Jiaqi Yao, Yukio Sasaki, Zhexing Wen, Gary J. Bassell, James Q. Zheng

NATURE NEUROSCIENCE 9 ( 10 ) 1265 - 1273 2006.10

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DOI： 10.1038/nn1773

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Regulation of dendritic branching and spine maturation by semaphorin3A-fyn signaling Reviewed

A Morita, N Yamashita, Y Sasaki, Y Uchida, O Nakajima, F Nakamura, T Yagi, M Taniguchi, H Usui, R Katoh-Semba, K Takei, Y Goshima

JOURNAL OF NEUROSCIENCE 26 ( 11 ) 2971 - 2980 2006.3

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DOI： 10.1523/JNEUROSCI.5453-05.2006

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Effects of ketamine and propofol on inflammatory responses of primary glial cell cultures stimulated with lipopolysaccharide Reviewed

YS Shibakawa, Y Sasaki, Y Goshima, N Echigo, Y Kamiya, K Kurahashi, Y Yamada, T Andoh

BRITISH JOURNAL OF ANAESTHESIA 95 ( 6 ) 803 - 810 2005.12

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DOI： 10.1093/bja/aei256

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Semaphorin3A signalling is mediated via sequential Cdk5 and GSK3 beta phosphorylation of CRMP2: implication of common phosphorylating mechanism underlying axon guidance and Alzheimer's disease Reviewed

Y Uchida, T Ohshima, Y Sasaki, H Suzuki, S Yanai, N Yamashita, F Nakamura, K Takei, Y Ihara, K Mikoshiba, P Kolattukudy, J Honnorat, Y Goshima

GENES TO CELLS 10 ( 2 ) 165 - 179 2005.2

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DOI： 10.1111/j.1365-2443.2005.00827.x

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Correlation between semaphorin3A-induced facilitation of axonal transport and local activation of a translation initiation factor eukaryotic translation initiation factor 4E

CX Li, Y Sasaki, K Takei, H Yamamoto, M Shouji, Y Sugiyama, T Kawakami, F Nakamura, T Yagi, T Ohshima, Y Goshima

JOURNAL OF NEUROSCIENCE 24 ( 27 ) 6161 - 6170 2004.7

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DOI： 10.1523/JNEUROSCI.1476-04.2004

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Cdk5/p35 and Rho-kinase mediate ephrin-A5-induced signaling in retinal ganglion cells Reviewed

Q Cheng, Y Sasaki, M Shoji, Y Sugiyama, H Tanaka, T Nakayama, N Mizuki, F Nakamura, K Takei, Y Goshima

MOLECULAR AND CELLULAR NEUROSCIENCE 24 ( 3 ) 632 - 645 2003.11

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DOI： 10.1016/S1044-7431(03)00220-3

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Control of growth cone motility and morphology by LIM kinase and slingshot via phosphorylation and dephosphorylation of cofilin Reviewed

M Endo, K Ohashi, Y Sasaki, Y Goshima, R Niwa, T Uemura, K Mizuno

JOURNAL OF NEUROSCIENCE 23 ( 7 ) 2527 - 2537 2003.4

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Fyn and Cdk5 mediate Semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex Reviewed

Y Sasaki, C Cheng, Y Uchida, O Nakajima, T Ohshima, T Yagi, M Taniguchi, T Nakayama, R Kishida, Y Kudo, S Ohno, F Nakamura, Y Goshima

NEURON 35 ( 5 ) 907 - 920 2002.8

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DOI： 10.1016/S0896-6273(02)00857-7

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Involvement of nitric oxide production via kynurenic acid-sensitive glutamate receptors in DOPA-induced depressor responses in the nucleus tractus solitarii of anesthetized rats Reviewed

K Yamanashi, T Miyamae, Y Sasaki, M Maeda, H Hirano, Y Misu, Y Goshima

NEUROSCIENCE RESEARCH 43 ( 3 ) 231 - 238 2002.7

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DOI： 10.1016/S0168-0102(02)00037-8

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Semaphorins as signals for cell repulsion and invasion Reviewed

Y Goshima, T Ito, Y Sasaki, F Nakamura

JOURNAL OF CLINICAL INVESTIGATION 109 ( 8 ) 993 - 998 2002.4

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Language：English Publishing type：Research paper (scientific journal) Publisher：AMER SOC CLINICAL INVESTIGATION INC

Goshima Y, Ito T, Sasaki Y, Nakamura F, The Journal of clinical investigation, 2002, vol. 109, no. 8, pp. 993-998, 2002

DOI： 10.1172/JCI200215467

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Semaphorins as signals for cell repulsion and invasion Reviewed

Yoshio Goshima, Takaaki Ito, Yukio Sasaki, Fumio Nakamura

Journal of Clinical Investigation 109 ( 8 ) 993 - 998 2002

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Language：English Publisher：The American Society for Clinical Investigation

DOI： 10.1172/JCI0215467

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Involvement of ionotropic glutamate receptors and nitric oxide in DOPA-induced depressor responses in the nucleus tractus solitarii Reviewed

Y Goshima, K Yamanashi, T Miyamae, Y Sasaki, M Maeda, H Hirano, Y Misu

CATECHOLAMINE RESEARCH: FROM MOLECULAR INSIGHTS TO CLINICAL MEDICINE 53 293 - 296 2002

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LIMキナーゼ1による神経成長円錐の形態制御機構

大橋一正, 遠藤光晴, 佐々木幸生, 五嶋良郎, 水野健作

神経化学 40 ( 2-3 ) 269 - 269 2001.9

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Language：Japanese Publisher：(一社)日本神経化学会

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Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse Reviewed

H Aizawa, S Wakatsuki, A Ishii, K Moriyama, Y Sasaki, K Ohashi, Y Sekine-Aizawa, A Sehara-Fujisawa, K Mizuno, Y Goshima, Yahara, I

NATURE NEUROSCIENCE 4 ( 4 ) 367 - 373 2001.4

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DOPA cyclohexyl ester, a competitive DOPA antagonist, protects glutamate release and resultant delayed neuron death by transient ischemia in hippocampus CA1 of conscious rats Reviewed

N Arai, N Furukawa, T Miyamae, Y Goshima, Y Sasaki, E Ohshima, F Suzuki, K Fujita, Y Misu

NEUROSCIENCE LETTERS 299 ( 3 ) 213 - 216 2001.2

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Autoradiographic studies using L-[C-14]DOPA and L-[H-3]DOPA reveal regional NA(+)-dependent uptake of the neurotransmitter candidate L-DOPA in the CNS Reviewed

Y Sugaya, Y Sasaki, Y Goshima, K Kitahama, T Kusakabe, T Miyamae, T Kato, Y Misu

NEUROSCIENCE 104 ( 1 ) 1 - 14 2001

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Cloning and characterization of the Caenorhabditis elegans CeCRMP/DHP-1 and -2; common ancestors of CRMP and dihydropyrimidinase? Reviewed

T Takemoto, Y Sasaki, N Hamajima, Y Goshima, M Nonaka, H Kimura

GENE 261 ( 2 ) 259 - 267 2000.12

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DOI： 10.1016/S0378-1119(00)00494-7

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Repulsive axon guidance molecule Sema3A inhibits branching morphogenesis of fetal mouse lung Reviewed

T Ito, M Kagoshima, Y Sasaki, CX Li, N Udaka, T Kitsukawa, H Fujisawa, M Taniguchi, T Yagi, H Kitamura, Y Goshima

MECHANISMS OF DEVELOPMENT 97 ( 1-2 ) 35 - 45 2000.10

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Effect of a novel bifunctional endothelin receptor antagonist, IRL 3630A, on guinea pig respiratory mechanics Reviewed

M Makatani, Y Fujitani, M Takimoto, K Oda, Y Sasaki, S Hori, T Inui, J Sakaki, T Okada, K Hoshiko, T Yamamura

EUROPEAN JOURNAL OF PHARMACOLOGY 406 ( 1 ) 139 - 147 2000.10

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Involvement of rBAT in Na+-dependent and -independent transport of the neurotransmitter candidate L-DOPA in Xenopus laevis oocytes injected with rabbit small intestinal epithelium poly A(+) RNA Reviewed

H Ishii, Y Sasaki, Y Goshima, Y Kanai, H Endou, D Ayusawa, H Ono, T Miyamae, Y Misu

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1466 ( 1-2 ) 61 - 70 2000.6

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Functions of semaphorins in axon guidance and neuronal regeneration Reviewed

Y Goshima, Y Sasaki, T Nakayama, T Ito, T Kimura

JAPANESE JOURNAL OF PHARMACOLOGY 82 ( 4 ) 273 - 279 2000.4

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Microautoradiography of L-[H-3]DOPA uptake sites in the rat brain Reviewed

Y Sugaya, Y Sasaki, Y Goshima, T Kusakabe, T Kato, Y Misu

FRONTIERS OF THE MECHANISMS OF MEMORY AND DEMENTIA ( 1200 ) 41 - 42 2000

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Functional mapping of L-DOPAergic systems in the CNS Reviewed

Y Goshima, Y Sasaki, H Ishii, Y Sugaya, M Shimizu, M Shimamura, Y Kuroiwa, T Miyamae, Y Misu

CONTROL AND DISEASES OF SODIUM DEPENDENT TRANSPORT PROTEINS AND ION CHANNELS 1208 387 - 390 2000

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Growth cone neuropilin-1 mediates collapsin-1/Sema III facilitation of antero- and retrograde axoplasmic transport Reviewed

Y Goshima, H Hori, Y Sasaki, T Yang, M Kagoshima-Maezono, CX Li, T Takenaka, F Nakamura, T Takahashi, SM Strittmatter, Y Misu, T Kawakami

JOURNAL OF NEUROBIOLOGY 39 ( 4 ) 579 - 589 1999.6

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DOI： 10.1002/(SICI)1097-4695(19990615)39:4<579::AID-NEU11>3.0.CO;2-9

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Selective activation of excitation-contraction coupling pathways by ETA and ETB receptors in guinea-pig tracheal smooth muscle Reviewed

T Inui, H Ninomiya, Y Sasaki, M Makatani, Y Urade, T Masaki, T Yamamura

BRITISH JOURNAL OF PHARMACOLOGY 126 ( 4 ) 893 - 902 1999.2

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DOI： 10.1038/sj.bjp.0702365

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A DOPA antagonist, DOPA cyclohexyl ester inhibits transient brain ischemia-induced release of glutamate and delayed neuronal cell death in striatal and hippocampal region of in vivo rats Reviewed

Y. Goshima, N. Furukawa, N. Arai, T. Miyamae, Y. Sasaki, M. Hashimoto, I. Yamamoto, K. Fujita, A. Akaike, Y. Misu

Folia Pharmacologica Japonica 114 ( 1 ) 1999

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Low-density induced apoptosis of cortical neurons is inhibited by serum factors Reviewed

Y Sasaki, N Fukushima, A Yoshida, H Ueda

CELLULAR AND MOLECULAR NEUROBIOLOGY 18 ( 5 ) 487 - 496 1998.10

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DOI： 10.1023/A:1026375225275

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Both ETA and ETB receptors are involved in mitogen-activated protein kinase activation and DNA synthesis of astrocytes: study using ETB receptor-deficient rats (aganglionosis rats) Reviewed

Y Sasaki, S Hori, K Oda, T Okada, M Takimoto

EUROPEAN JOURNAL OF NEUROSCIENCE 10 ( 9 ) 2984 - 2993 1998.9

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DOI： 10.1111/j.1460-9568.1998.00305.x

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Regulation of inducible NO synthase expression by endothelin in primary cultured glial cells Reviewed

T Murayama, H Oda, Y Sasaki, T Okada, Y Nomura

LIFE SCIENCES 62 ( 17-18 ) 1491 - 1495 1998.3

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DOI： 10.1016/S0024-3205(98)00095-2

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Endothelin enhances lipopolysaccharide-induced expression of inducible nitric oxide synthase in rat glial cells Reviewed

H Oda, T Murayama, Y Sasaki, T Okada, Y Nomura

EUROPEAN JOURNAL OF PHARMACOLOGY 339 ( 2-3 ) 253 - 260 1997.11

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DOI： 10.1016/S0014-2999(97)01369-1

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Endothelin evokes efflux of glutamate in cultures of rat astrocytes Reviewed

Y Sasaki, M Takimoto, K Oda, T Fruh, M Takai, T Okada, S Hori

JOURNAL OF NEUROCHEMISTRY 68 ( 5 ) 2194 - 2200 1997.5

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DOI： 10.1046/j.1471-4159.1997.68052194.x

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Endothelin-A receptor-mediated prostanoid secretion via autocrine and deoxyribonucleic acid synthesis via paracrine signaling in human bronchial epithelial cells Reviewed

M Takimoto, K Oda, Y Sasaki, T Okada

ENDOCRINOLOGY 137 ( 11 ) 4542 - 4550 1996.11

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ET(A) and ET(B) receptors cooperate in DNA synthesis via opposing regulations of cAMP in human lung cell line Reviewed

M Takimoto, K Oda, T Fruh, M Takai, T Okada, Y Sasaki

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY 271 ( 3 ) L366 - L373 1996.9

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PROTEIN-KINASE-C INVOLVEMENT IN HOMOLOGOUS DESENSITIZATION OF DELTA-OPIOID RECEPTOR-COUPLED TO G(I1)-PHOSPHOLIPASE C ACTIVATION IN XENOPUS OOCYTES Reviewed

H UEDA, T MIYAMAE, C HAYASHI, S WATANABE, N FUKUSHIMA, Y SASAKI, T IWAMURA, Y MISU

JOURNAL OF NEUROSCIENCE 15 ( 11 ) 7485 - 7499 1995.11

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OPIOID MU-RECEPTOR AND KAPPA-RECEPTOR MEDIATE PHOSPHOLIPASE-C ACTIVATION THROUGH GI1 IN XENOPUS OOCYTES Reviewed

H UEDA, T MIYAMAE, N FUKUSHIMA, H TAKESHIMA, K FUKUDA, Y SASAKI, Y MISU

MOLECULAR BRAIN RESEARCH 32 ( 1 ) 166 - 170 1995.8

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POTENTIAL ROLE OF PHOSPHOLIPASE-A2 IN HL-60 CELL-DIFFERENTIATION TO MACROPHAGES INDUCED BY PROTEIN-KINASE-C ACTIVATION Reviewed

Y ASAOKA, K YOSHIDA, Y SASAKI, Y NISHIZUKA

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 90 ( 11 ) 4917 - 4921 1993.6

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DOI： 10.1073/pnas.90.11.4917

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POTENTIATION OF DIACYLGLYCEROL-INDUCED ACTIVATION OF PROTEIN-KINASE-C BY LYSOPHOSPHOLIPIDS - SUBSPECIES DIFFERENCE Reviewed

Y SASAKI, Y ASAOKA, Y NISHIZUKA

FEBS LETTERS 320 ( 1 ) 47 - 51 1993.3

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DOI： 10.1016/0014-5793(93)81655-J

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POSSIBLE ROLE OF MAMMALIAN SECRETORY GROUP-II PHOSPHOLIPASE-A2 IN LYMPHOCYTE-T ACTIVATION - IMPLICATION IN PROPAGATION OF INFLAMMATORY REACTION Reviewed

Y ASAOKA, K YOSHIDA, Y SASAKI, Y NISHIZUKA, M MURAKAMI, KUDO, I, K INOUE

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 90 ( 2 ) 716 - 719 1993.1

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DOI： 10.1073/pnas.90.2.716

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PROTEIN-KINASE-C FOR CELL SIGNALING - A POSSIBLE LINK BETWEEN PHOSPHOLIPASES Reviewed

S NAKAMURA, Y ASAOKA, K YOSHIDA, Y SASAKI, Y NISHIZUKA

CELL SIGNALLING : BIOLOGY AND MEDICINE OF SIGNAL TRANSDUCTION 28 171 - 178 1993

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ROLE OF LYSOPHOSPHATIDYLCHOLINE IN LYMPHOCYTE-T ACTIVATION - INVOLVEMENT OF PHOSPHOLIPASE-A2 IN SIGNAL TRANSDUCTION THROUGH PROTEIN-KINASE-C Reviewed

Y ASAOKA, M OKA, K YOSHIDA, Y SASAKI, Y NISHIZUKA

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 89 ( 14 ) 6447 - 6451 1992.7

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DOI： 10.1073/pnas.89.14.6447

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EFFICIENT INVITRO FOLDING OF THE 3-DISULFIDE DERIVATIVES OF HEN LYSOZYME IN THE PRESENCE OF GLYCEROL Reviewed

H SAWANO, Y KOUMOTO, K OHTA, Y SASAKI, SI SEGAWA, H TACHIBANA

FEBS LETTERS 303 ( 1 ) 11 - 14 1992.5

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Cyclin Dependent Kinase 5 (Cdk5)

Nancy Y. Ip, Li-Huei Tsai

Springer 2008.8 （ ISBN:0387788867 ）

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脆弱X精神遅滞タンパク質のRNA結合ドメインは液-液相分離が関与する神経輸送顆粒の形成に重要である

吉澤佳那恵, 久保萌々, 石山真帆, 佐々木幸生

日本分子生物学会年会プログラム・要旨集(Web) 48th 2025

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脆弱X精神遅滞タンパク質におけるRNA結合ドメインがストレス顆粒と神経輸送顆粒形成に与える役割

久保萌々, 石山真帆, 吉澤佳那恵, 佐々木幸生

日本生物学的精神医学会(Web) 46th 2024

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神経細胞のスパインの成熟における脆弱X精神遅滞タンパク質のRNA顆粒形成の役割

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日本生物学的精神医学会(Web) 46th 2024

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大規模言語モデルを用いた液-液相分離関連論文からの情報抽出手法の開発

陳佳盈, 石田祥一, 佐々木幸生, 寺山慧

日本蛋白質科学会年会(Web) 24th 2024

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RNA granules and RNA transport/local translation in neurons Invited

Yoshinari Fujiwara, Yukio Sasaki

The Cell 54 ( 8 ) 478 - 482 2022.7

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Manipulation of fragile X mental retardation protein-containing granule formation in neurons by optogenetic control of liquid-liquid phase separation

藤原睦也, 佐々木幸生

日本分子生物学会年会プログラム・要旨集(Web) 45th 2022

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Overexpression of RNA-binding domain-deficient mutant of Fragile X mental retardation protein suppresses RNA granule formation

藤原睦也, 佐々木幸生

日本分子生物学会年会プログラム・要旨集(Web) 44th 2021

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マイクロRNA382のエクソソームを介した分泌機構と標的遺伝子の解析

木村貴洋, 田中智美, 佐々木幸生

日本薬理学雑誌 151 ( Supplement ) 2018

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人工誘導プレシナプスを用いた神経活動計測系の開発

武田怜之雅, PARVIN Shumaia, 佐々木幸生

日本薬理学雑誌 150 ( Supplement ) 2017

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大脳皮質神経細胞培養系において脱分極刺激により特定のマイクロRNAがエクソソーム中に増加する

田中智美, 高橋徹, 佐々木幸生

日本薬理学会関東部会プログラム・要旨集 134th 2016

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脆弱X精神遅滞タンパク質に対するユビキチンリガーゼの同定の試み

高畠将, 高橋徹, 梁明秀, 五嶋良郎, 佐々木幸生

日本分子生物学会年会プログラム・要旨集(Web) 39th 2016

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シナプス前終末形成過程におけるマイクロRNA結合タンパク質Argonaute2の局在変化

高橋徹, 杉浦侑, 佐々木幸生

日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 88回・38回 [3P1323] - [3P1323] 2015.12

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セマフォリン3Aは脆弱X精神遅滞タンパク質のユビキチン化を誘導する

高畠将, 五嶋良郎, 佐々木幸生

日本薬理学会関東部会プログラム・要旨集 130th 2014

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翻訳から分子シャペロンへ生理機能と病態翻訳トランス因子による軸索局所翻訳制御と神経疾患との関連

佐々木幸生

日本生理学雑誌 75 ( 6 ) 62 - 63 2013.11

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中枢神経系におけるドーパ受容体候補分子OA1の発現分布

神谷真梨奈, 山下直也, 佐々木幸生, 中村史雄, 五嶋良郎

日本薬理学雑誌 141 ( 1 ) 16P - 16P 2013.1

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セマフォリン3Aによる脆弱X精神遅滞タンパク質の局在制御

高畠将, 五嶋良郎, 佐々木幸生

日本RNA学会年会要旨集 15th 2013

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セマフォリン3Aによる脆弱X精神遅滞タンパク質の成長円錐内局在制御におけるユビキチン化の役割

高畠将, 五嶋良郎, 佐々木幸生

日本分子生物学会年会プログラム・要旨集(Web) 36th 2013

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Regulation of Local Translation for Neuronal Functions in Axons and Growth Cones

31 ( 6 ) 677 - 682 2012.5

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DOI： 10.15105/j01677.2012267058

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Immunohistochemical examination of OA1, a receptor candidate for L-3,4-dihydroxyphenylalanine, in the CNS

Marina Kamiya, Naoya Yamashita, Yukio Sasaki, Fumio Nakamura, Yoshio Goshima

JOURNAL OF PHARMACOLOGICAL SCIENCES 118 134P - 134P 2012

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神経軸索におけるマイクロRNAオミクスにより同定されたmiRNA-720は神経栄養因子による軸索伸長に関与する

佐々木幸生, 佐々木幸生, XING Lei, GROSS Christina, 五嶋良郎, BASSELL Gary J.

日本RNA学会年会要旨集 14th 2012

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新規培養法「ニューロンボール法」を用いたシナプス前終末分化過程の軸索のプロテオーム解析

佐々木幸生, 石川晃代, 川上隆雄, 川上隆雄, 平野久, 五嶋良郎

日本分子生物学会年会プログラム・要旨集(Web) 35th 2012

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神経軸索マイクロRNAプロファイリングにより同定されたマイクロRNA-720は神経栄養因子刺激により成長円錐に集積する

佐々木幸生, Xing Lei, Gross Christina, 五嶋良郎, Bassell Gray J.

日本生化学会大会プログラム・講演要旨集 84回 4T16p - 10 2011.9

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Brain-derived neurotrophic factor regulates localization of microRNA-720 in growth cones

Yukio Sasaki, Lei Xing, Christina Gross, Yoshio Goshima, Gary J. Bassell

NEUROSCIENCE RESEARCH 71 E224 - E225 2011

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DOI： 10.1016/j.neures.2011.07.978

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Identification of microRNAs enriched in axons and growth cones

Yukio Sasaki, Gary J. Basse, Lei Xing, Christina Gross, Yoshio Goshima

JOURNAL OF PHARMACOLOGICAL SCIENCES 115 240P - 240P 2011

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Semaphorin3A facilitates the axonal transport of PlexinA4 through interaction of PlexinA4 with TrkA

Masayuki Yamane, Naoya Yamashita, Yukio Sasaki, Fumio Nakamura, Yoshio Goshima

NEUROSCIENCE RESEARCH 71 E119 - E119 2011

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DOI： 10.1016/j.neures.2011.07.507

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軸索に豊富に局在するマイクロRNAのプロファイリング(Profiling of microRNAs enriched in axons)

佐々木幸生, Xing Lei, Gross Christina, 五嶋良郎, Bassell Gary J.

神経化学 49 ( 2-3 ) 704 - 704 2010.8

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Profiling of microRNAs enriched in axons

Yukio Sasaki, Lei Xing, Christina Gross, Yoshio Goshima, Gary J. Bassell

NEUROSCIENCE RESEARCH 68 E354 - E354 2010

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DOI： 10.1016/j.neures.2010.07.1570

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Semaphorin3A selectively facilitates the axonal transport of its receptor and intracellular signaling molecules

Naoya Yamashita, Taiichirou Gotoh, Hiroshi Usui, Aiko Yamamoto, Yukio Sasaki, Fumio Nakamura, Kohtaro Takei, Yoshio Goshima

JOURNAL OF PHARMACOLOGICAL SCIENCES 106 91P - 91P 2008

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RNAと神経疾患

佐々木幸生, BASSELL Gary J

Clin Neurosci 24 ( 8 ) 950-951 2006.8

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Semaphorin3A selectively facilitates the axonal transport of its receptor and intracellular signaling molecules

N Yamashita, T Gotoh, H Usui, A Yamamoto, Y Sasaki, F Nakamura, K Takei, Y Goshima

JOURNAL OF PHARMACOLOGICAL SCIENCES 100 117P - 117P 2006

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大脳皮質ニューロンのspine形成及びbranch形成における軸索ガイド分子Sema3Aの役割(Role of Sema3A in dendritic branching and spine formation of mouse cortical neurons)

森田麻, 竹居光太郎, 佐々木幸生, 内田穣, 中島央美, 中村史雄, 五嶋良郎

神経化学 43 ( 2-3 ) 520 - 520 2004.8

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Correlation between semaphorin3A-induced facilitation of axonal transport and local activation of a translation initiation factor eukaryotic translation initiation factor 4E

CX Li, Y Sasaki, K Takei, H Yamamoto, M Shouji, Y Sugiyama, T Kawakami, F Nakamura, T Yagi, T Ohshima, Y Goshima

JOURNAL OF NEUROSCIENCE 24 ( 27 ) 6161 - 6170 2004.7

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DOI： 10.1523/JNEUROSCI.1476-04.2004

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Role of local protein synthesis within nerve growth cone in Sema3A-induced neurite retraction and NGF-induced neurite outgrowth

Kohtaro Takei, Chanxia Li, Kumiko Sengoku, Yukio Sasaki, Furnio Nakamura, Yoshio Goshima

CELL STRUCTURE AND FUNCTION 29 21 - 21 2004.5

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Signaling at the growth cone and regenerative medicine

Y Goshima, Y Sasaki, F Nakamura, KI Ogura, K Takei

JOURNAL OF PHARMACOLOGICAL SCIENCES 94 42P - 42P 2004

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Phosphorylation of CRMPs by Cdk5 plays a critical role in Semaphorin-3A signaling.

Y Uchida, Y Sasaki, T Fuchikawa, F Nakamura, Y Goshima

JOURNAL OF PHARMACOLOGICAL SCIENCES 91 127P - 127P 2003

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大脳皮質ニューロンのspine及びbranch形成における軸索ガイド分子Sema3Aの役割

森田麻, 佐々木幸生, 内田穣, 中島央美, 中村史雄, 竹居光太郎, 五嶋良郎

日本分子生物学会年会プログラム・講演要旨集 26th 2003

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細胞骨格・細胞運動制御の情報伝達神経軸索誘導の分子機序セマフォリンファミリーを中心に

佐々木幸生, 五嶋良郎

月刊メディカル・サイエンス・ダイジェスト 28 ( 13 ) 525 - 529 2002.12

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神経ガイド分子セマフォリン-3AはFyn-Cdk5キナーゼカスケードを介して大脳皮質神経回路網形成を制御する

佐々木幸生, 五嶋良郎

細胞工学 21 ( 11 ) 1324 - 1325 2002.10

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Isolation and characterization of a receptor candidate for L-DOPA in Caenorhabditis elegans

Y Goshima, T Miyamae, M Ibi, F Nakamura, Y Sasaki, K Ogura, T Ishihara, Y Misu, Katsura, I

JAPANESE JOURNAL OF PHARMACOLOGY 88 157P - 157P 2002

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Extension control mechanism of the retina ganglion cell of ephrin A5.

CHENG C, 佐々木幸生, 水木信久, 大野重昭, 五嶋良郎

横浜市特定研究事業報告書平成13年度老化と機能保持再生に関する研究研究班 2002

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セマフォリン3Aシグナルは大脳皮質錐体細胞における樹状突起の形態形成に関与する

五嶋良郎, 佐々木幸生, 森田麻, 大島登志男, 八木健, 谷口雅彦, 中村史雄, 岸田令次

日本神経科学大会プログラム・抄録集 25th 2002

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海馬神経細胞と後根神経節細胞のSema3A作用による応答の相違

庄司雅幸, 佐々木幸生, 堀英明, 李蝉夏, 五嶋良郎

日本神経科学大会プログラム・抄録集 25th 2002

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線虫ドーパ受容体候補分子の単離・同定

衣斐督和, 宮前丈明, 中村史雄, 佐々木幸生, 小倉顕一, 石原健, 桂勲, 三須良実, 五嶋良郎

日本神経科学大会プログラム・抄録集 25th 2002

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Ephrin-A5が神経細胞と非神経細胞の形態学的変化を誘導する,Cdk5/P35依存性あるいは非依存性経路(Cdk5/P35-dependent and Independent Pathways through Which ephrin-A5 Induces Morphological Changes of Neuronal and Non-neuronal Cells)

Cheng Chi, 佐々木幸生, 中山孝, 田中英明, 大野重昭, 五嶋良郎

神経化学 40 ( 2-3 ) 269 - 269 2001.9

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セマフォリン3A情報伝達はFyn-Cdk5リン酸化カスケードを介する

佐々木幸生, Cheng Chi, 内田穣, 大島登志男, 八木健, 谷口雅彦, 中山孝, 工藤佳久, 大野重昭, 中村史雄

神経化学 40 ( 2-3 ) 269 - 269 2001.9

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セマフォリン3A情報伝達におけるFyn-Cdk5リン酸化カスケードの役割

佐々木幸生, Cheng Chi, 内田穣, 大島登志男, 八木健, 谷口雅彦, 中山孝, 工藤佳久, 大野重昭, 中村史雄

生化学 73 ( 8 ) 918 - 918 2001.8

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Aging and pathophysiological role of neurotransmitter dopa. Dopa is death control factor of ischemic nerve cell and pressure control factor. ( Yokohama City Univ. school of medicine ).

五嶋良郎, 古川信也, 橋本瑞樹, 宮前丈明, 佐々木幸生, 藤田浄秀, 山本勇夫

横浜市特定研究事業報告書平成10-12年度脳・神経系の老化に関する総合的研究 52 ( 3 ) 252 - 252 2001.5

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Signal Transduction Systems for Axon Guidance Molecules.

佐々木幸生, 五嶋良郎

細胞工学 20 ( 4 ) 530 - 537 2001.4

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線虫Caenorhabditis elegansの行動に及ぼすL-DOPAの作用及びL-DOPA応答異常変異株の単離とその解析

五嶋良郎, 塚本信也, 佐々木幸生, 朝倉太郎, 石原健, 小倉顕一, 桂勲

日本薬理学雑誌 117 ( 3 ) 51P - 51P 2001.3

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LIMキナーゼ1による神経成長円錐の形態制御機構

大橋一正, 遠藤光晴, 佐々木幸生, 五嶋良郎, 水野健作

日本神経科学大会プログラム・抄録集 24th 2001

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セマフォリン3A情報伝達はFyn-Cdk5リン酸化カスケードを介する

佐々木幸生, 大島登志男, 八木健, 谷口雅彦, 中山孝, 工藤佳久, 大野重昭, 中村史雄, 五嶋良郎

日本神経科学大会プログラム・抄録集 24th 2001

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LIMキナーゼ1による神経成長円錐の形態抑制機構

大橋一正, 遠藤光晴, 佐々木幸生, 五嶋良郎, 水野健作

神経化学 40 ( 2/3 ) 2001

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孤束核微量注入DOPAの降圧応答におけるグルタミン酸,NO系の関与

月見里薫, 宮前丈明, 佐々木幸生, 三須良實, 五嶋良郎

日本薬理学雑誌 116 ( 4 ) 70P - 70P 2000.10

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Sema3AはNeuropilin-1とLavendustin A感受性Tyrosine Kinaseを介して後根神経節軸索輸送を促進する

李蝉夏, 堀英明, 佐々木幸生, 川上倫, 石川義弘, 五嶋良郎

日本神経科学大会プログラム・抄録集 23rd 2000

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膜結合型セマフォリンとその機能

木村徹, 菊地薫, 林剛史, 中村史雄, 佐々木幸生, 五嶋良郎

神経化学 39 ( 3 ) 2000

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リムキナーゼによるコフィリンのリン酸化は,セマフォリン3Aによる神経成長円錐の葉状突起崩壊に必要十分である

藍沢広行, 佐々木幸生, 若月修二, 森山賢治, 石井愛, 藤沢淳子, 五嶋良郎, 矢原一郎

生化学 72 ( 8 ) 2000

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リムキナーゼによるコフィリンのリン酸化は,セマフォリン3Aによる神経成長円錐の葉状突起崩壊に必要である

藍沢広行, 若月修二, 石井愛, 森山賢治, 佐々木幸生, 大橋一正, 水野健作, 五嶋良郎, 矢原一郎

日本細胞生物学会大会講演要旨集 53rd 2000

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孤束核微量注入DOPAの降圧応答におけるグルタミン酸およびNO系の関与

宮前丈明, 月見里薫, 佐々木幸生, 三須良実, 五嶋良郎

日本神経科学大会プログラム・抄録集 23rd 2000

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Is dopa a cause of nerve cell death ? Glutamic acid liberation and nerve cell death response of dopa itself in corpus striatum. (Yokohama City Univ. medical school S).

三須良実, 五嶋良郎, 宮前丈明, 古川信也, 佐々木幸生

横浜市特定研究事業報告書平成10年度脳・神経系の老化に関する総合的研究 50 ( 5 ) 638 - 639 1999.9

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セマフォリンは発生期の肺の形態形成を制御する

鹿子島雅子, 伊藤隆明, 宇高直子, 佐々木幸生, 李蝉夏, 北村均, 五嶋良郎

生化学 71 ( 8 ) 1039 - 1039 1999.8

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リン酸化タウの神経成長円錐における機能

中山孝, 五嶋良郎, 佐々木幸生, Cheng Chi, 大野重昭, 加藤尚彦

生化学 71 ( 8 ) 911 - 911 1999.8

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ラット脳切片標本におけるL-DOPA取り込み部位の検出

菅谷葉子, 佐々木幸生, 五嶋良郎, 日下部辰三, 加藤武, 三須良實

日本薬理学雑誌 113 ( 2 ) 27P - 27P 1999.2

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CeCRMP/DHP-1,2遺伝子の単離と遺伝子破壊による機能解析

竹本忠司, 佐々木幸生, 五嶋良郎, 浜嶋直樹, 木村博, 野中勝

日本発生生物学会大会発表要旨集 32nd 1999

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ラット脳におけるNa<sup>+</sup>依存性L-DOPA取り込み部位ミクロオートラジオグラフィーによる検索

菅谷葉子, 佐々木幸生, 五嶋良郎, 日下部辰三, 加藤武, 三須良実

日本神経科学大会プログラム・抄録集 22nd 1999

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SemaIII応答におけるチロシンリン酸化の関与

佐々木幸生, 野田恵, 程き, 堀英明, 川上倫, 石川義弘, 下仲基之, 大野重昭, 五嶋良郎

日本神経科学大会プログラム・抄録集 22nd 1999

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Cloning and characterization of CeCRMP/DRP-1, 2 genes of C. elegans.

TAKEMOTO Tadashi, SASAKI Yukio, GOSHIMA Yoshio, HAMAJIMA Naoki, KIMURA Hiroshi, NONAKA Masaru

21 667 - 667 1998.12

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軸索ガイダンスにおける成長円錐運動の分子機構神経・非神経細胞におけるSema D/collapsin-1シグナルの分子機構

五嶋良郎, 佐々木幸生, 前園雅子

神経化学 37 ( 3 ) 266 - 266 1998.9

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コラプシン応答媒介分子CRMP-62の線虫ホモログCeCRMP-1及びCeCRMP-2の同定と発現分布

佐々木幸生, 五嶋良郎

神経化学 37 ( 3 ) 552 - 552 1998.9

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アフリカツメガエル卵母細胞発現系を用いたNa+依存性L-DOPA輸送活性の解析

石井大之, 五嶋良郎, 佐々木幸生, 鮎沢大, 金井好克, 遠藤仁, 三須良實

神経化学 37 ( 3 ) 489 - 489 1998.9

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ラット脳グリア細胞におけるinducible NOS(iNOS)誘導に対するendothelin(ET)の作用

小田温子, 村山俊彦, 佐々木幸生, 岡田敏一, 野村靖幸

神経化学 35 ( 3 ) 562 - 563 1996.9

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Reconfiguration experiment on opioid .KAPPA. acceptor and various G proteins using baculovirus manifestation system.

河野雅之, 福嶋伸之, 三須良実, 川本進, 加藤武, 佐々木幸生, 岡田敏一, 芳賀達也, 植田弘師

日本分子生物学会年会プログラム・講演要旨集 19 ( 0 ) 324 - 324 1996.8

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エンドセリンはアストロサイトからのグルタミン酸の逆行性輸送を促進する.

佐々木幸生, 瀧本京, 大前恭子, FRUEH Thomas, 高井道博, 岡田敏一, 堀清次

日本分子生物学会年会プログラム・講演要旨集 19 ( 0 ) 353 - 353 1996.8

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ヒトグリオブラストーマU-138に発現させたグルタミン酸トランスポーターの性質と活性の調節

堀清次, 佐々木幸生, 滝本京, 大前恭子, 川上秀史, 田中光一, 岡田敏一

日本分子生物学会年会プログラム・講演要旨集 19 ( 0 ) 353 - 353 1996.8

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エンドセリン受容体サブタイプ特異的抗体の作成

瀧本京, 堀清次, 佐々木幸生, 大前恭子, 岡田敏一

日本分子生物学会年会プログラム・講演要旨集 19 ( 0 ) 155 - 155 1996.8

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<Abstract of published report>Protein Kinase C Involvement in Homologous Desensitization of δ-Opioid Receptor Coupled to G_<i1>-Phospholipase C Activation in Xenopus Oocytes

UEDA HIROSHI, MIYAMAE TAKEAKI, HAYASHI CHIFUMI, WATANABE SHIGERU, FUKUSHIMA NOBUYUKI, SASAKI YUKIO, IWAMURA TATSUNORI, MISU YOSHIMI

The annual proceedings of Gifu College of Pharmacy 45 68 - 68 1996.6

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無血清培養下に認められる大脳皮質神経細胞の密度依存的な生存維持と血清添加の影響

佐々木幸生

生化学 67 ( 7 ) 849 - 849 1995.7

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Receptors of the nervous systems - update.Functional regulation and plasticity by phosphorylation of nervous system receptors.

SASAKI YUKIO, UEDA HIROSHI

Clin Neurosci 13 ( 5 ) 529-534 1995.5

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THE INDUCTION OF ENDOTHELIN RECEPTORS AND THE MODIFICATION OF ENDOTHELIN-INDUCED RESPONSES BY INTERLEUKIN-1-BETA IN PRIMARY CULTURED SMOOTH-MUSCLE CELLS FROM HUMAN AORTA

Y FUJITANI, Y SASAKI, T OKADA, Y URADE

JOURNAL OF CELLULAR BIOCHEMISTRY 267 - 267 1994.1

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Industrial property rights

可溶性ニューロピリン

五嶋良郎, 佐々木幸生

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Application no：特願平11-038920 Date applied：1999.2

Announcement no：特開2000-236879 Date announced：2000.9

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Mechanism of formation of neuronal transport granules and their role in axon elongation and synaptogenesis - relationship to phase separation

Grant number：23K05964 2023.4 - 2026.3

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

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Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

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RNA granule-mediated regulation for local translation and presynapse formation: relation between phase separation and synapse granules

Grant number：20K06877 2020.4 - 2023.3

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Yukio Sasaki

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Grant amount：\4420000 （ Direct Cost: \3400000 、 Indirect Cost：\1020000 ）

Fragile X Mental Retardation Protein (FMRP) is a component of RNA granules, including stress granules. Our study suggests that FMRP, in conjunction with other RNA-binding proteins, forms RNA granules and regulates local translation in the presynapses of neuronal axons. FMRP-deficient neurons demonstrated elevated local translation and increased synaptic vesicle secretion. However, in metformin-treated FMRP-deficient neurons, translation was suppressed, and synaptic vesicle secretion was reduced to levels observed in wild types. We developed an optogenetic system to control RNA granule formation, where blue light irradiation prompts liquid-liquid phase separation, enabling spatial and temporal regulation of FMRP-containing RNA granules. Using this system, we plan to clarify the mechanisms through which RNA granule formation influences synaptic morphology and functions.

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Regulation of neural circuit by Fragile X Mental Retardation Protein - its relation to ubiquitination and local translation

Grant number：16K07061 2016.4 - 2019.3

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Yukio Sasaki, Ito Hidenori

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Grant amount：\4940000 （ Direct Cost: \3800000 、 Indirect Cost：\1140000 ）

The role of fragile X mental retardation protein (FMRP) in axon guidance and synapse formation during neural circuit formation was examined in relation to ubiquitination and local translation. Our results suggest that after stimulation with the axon guidance molecule Sema3A, FMRP was degraded in growth cones by the ubiquitin-proteasome system, followed by that local translation was triggered to induce a morphological change of growth cones. We also identified the ubiquitination related gene for FMRP, and found that the gene product induced disappearance of FMRP after granular accumulation of FMRP. FMRP-containing granules were also observed during synapse formation. Therefore, our findings suggested that ubiquitination of FMRP is involved in neural circuit formation through regulation of granule formation and local translation of FMRP.

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Role of local protein synthesis regulated by Fragile X Mental Retardation Protein during presynapse formation

Grant number：25430068 2013.4 - 2016.3

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

SASAKI Yukio, KAWAKAMI Takao

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To investigate to a role of local protein synthesis during presynapse differentiation in neurons, we identified proteins that accumulate in axons during presynapse differentiation. Most of the identified proteins are derived from the target mRNA for FMRP (Fragile X Mental Retardation Proteins), the RNA-binding protein. Among these proteins, we examined Munc-18 accumulation during the presynapse differentiation. The accumulation time-course of Munc-18 corresponded to that of Argonaute2 (Ago2), which interacts with FMRP. Thus, it is possible that FMRP-Ago2 complex regulate Munc-18 expression via local protein synthesis during presynapse differentiation.

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マイクロＲＮＡの輸送マシナリーの解明と軸索機能における役割

Grant number：24115713 2012.4 - 2014.3

日本学術振興会科学研究費助成事業新学術領域研究(研究領域提案型)

佐々木幸生

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Authorship：Principal investigator Grant type：Competitive

Grant amount：\8970000 （ Direct Cost: \6900000 、 Indirect Cost：\2070000 ）

脆弱X症候群の原因遺伝子産物である脆弱X精神遅滞タンパク質 (Fragile X Mental Retardation Protein: FMRP) のマイクロRNA輸送機構の解明の目的で、大脳皮質神経細胞をニューロンボール法で培養し、FMRPの成長円錐内の挙動を解析した。軸索ガイダンス因子の一つであるセマフォリン3A (Sema3A) 刺激により成長円錐内のFMRPが減少するがAgo2は減少しなかった。このFMRP特異的減少は逆行性輸送に関与するダイニンの阻害剤であるEHNAでは阻害されないが、ユビキチンE1酵素阻害剤であるPYR-41、あるいはプロテアソーム阻害剤MG-132 で阻害されないことから、逆行性輸送ではなく、ユビキチン-プロテアソーム系によるFMRP特異的な分解が関与することが示唆された。さらに、Sema3A刺激により成長円錐内のユビキチン化が亢進することを抗ユビキチン化タンパク質抗体FK2による染色で確認した。我々が以前、軸索に局在することを報告したマイクロRNA-532 (miR-532) はFMRPと相互作用することがCLIP解析で報告されている。そこで、Sema3A刺激による同マイクロRNAの局在変化を解析した。Sema3A刺激がmiR-532の成長円錐内での局在を低下させる傾向が認められた。従って、FMRPのユビキチン-プロテアソーム系による分解がマイクロRNAを減少させ、翻訳を開始させる可能性が考えられる。

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Role of growth cone autonomy and translational trans-acting factors in axon guidance

Grant number：22500336 2010 - 2012

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

SASAKI Yukio, GOSHIMA Yoshio

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Authorship：Principal investigator Grant type：Competitive

Grant amount：\4290000 （ Direct Cost: \3300000 、 Indirect Cost：\990000 ）

We have investigated two mRNA-binding, translational trans-acting factors to regulate local translation in axonal growth cones in neurons. We demonstratedthat Zipcode-Binding Protein 1 (ZBP1), an mRNA-binding protein, regulates translation of β-actin mRNA, and then direction of axonal extension, via phosphorylation induced by Brain-Derived Neurotrophic Factor (BDNF). We also found that microRNAs (miRNAs), non-coding RNAs bind to mRNA, exist in growth cones. We indicate the possibility that axonal miRNAs are involved in axonal extension regulated by BDNF.

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The relation between LAR class protein tyrosine phosphates and Semaphorin-Plexin signaling

Grant number：13670128 2001 - 2002

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

NAKAMURA Fumio, OGURA Ken-ichi, SASAKI Yukio

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Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid) Grant type：Competitive

Grant amount：\4100000 （ Direct Cost: \4100000 ）

We have investigated whether LAR class Protein Tyrosine Phosphatase (PTP) is involved in Semaphorin-3A (Sema3A) signaling. In Drosophila, DLAR mutant exhibits 'bypass' phenotype of ISNb motoneuron projection that is observed in Dsemal and DPlexA mutants, suggesting the relation between the PTP and Semaphorin signaling. In mammals, LAR class PTP consists of LAR, PTP delta, and PTP sigma. We expressed a series of truncated mutant of these PTPs in chick dorsal root ganglions and tested Sema3A-induced growth cone collapse. We found that PTP delta mutants attenuated Sema3A signaling. To explore ...

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神経細胞死における成長円錐と細胞体のダイアログ

Grant number：13780619 2001 - 2002

日本学術振興会科学研究費助成事業若手研究(B)

佐々木幸生

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Authorship：Principal investigator Grant type：Competitive

Grant amount：\1800000 （ Direct Cost: \1800000 ）

我々は昨年度、神経回路ガイド分子であるセマフォリン3A (Sema3A)の情報伝達にチロシンキナーゼFynとセリン・トレオニンキナーゼCak5が関与することを報告した。今年度研究を遂行できたのは4〜8月の5ヶ月間であったが、その間の進展を報告する。我々はsema3A(-/-)とfyn(-/-)マウスの解析の結果、これらの遺伝子が大脳皮質第5層錐体細胞の樹状突起の伸長方向を決定するのに重要であることを見出した。このことより、神経軸索だけでなく、樹状突起におけるSema3Aの役割が注目された。培養海馬神経細胞にSema3Aを投与すると、軸索のみならず樹状突起においても細胞内粒子輸送の亢進が起こることが新たに見出された。この樹状突起における輸送の亢進は、Sema3Aを樹状突起に局所投与した場合には見られず、成長円錐に局所投与後約10分の遅れのあと観察された。軸索輸送の場合はSema3A刺激後すぐに亢進が始まることから考えると、Sema3Aが成長円錐を刺激した後、その情報が軸索、細胞体を通り樹状突起に達するまで10分程度かかることになる。現在、成長円錐から樹状突起への情報伝達を解析中である。また、Sema3A受容体であるプレキシン、ニューロピリンとGFPとの融合タンパク質を用い、軸索中での輸送を可視化し、fluorescent recovery after photobreach (...

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軸索伸長抑制因子Nogoの受容体同定とセマフォリンの細胞内情報伝達系の解明

Grant number：12210124 2000

日本学術振興会科学研究費助成事業特定領域研究(C)

中村史雄, 佐々木幸生

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Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid) Grant type：Competitive

Nogo受容体の性質:当初試みたパニング法ではNogo結合蛋白質は得られなかったが、アルカリホスファターゼ(AP)とNogo細胞外領域との融合蛋白質(APNext)をプローブに用いると、マウス胎仔17日大脳皮質由来の培養神経細胞に結合を認めた。別グループによりAPとNogoの融合蛋白質を用いた同様の手法でGPIアンカー型の膜蛋白質がNogo受容体として報告された。この受容体はAPNextにKd=7nM程度の親和性を持つ。しかしGPI部分を取りAP融合にした受容体はNogo全長を発現させたCOS-7細胞には結合しない。このように同定された受容体とリガンドとの関係はまだ明確でない。いくつかのクラス3セマフォリン(3A,3E)はC末端にある塩基性アミノ酸に富む領域を介してKd=30nM程度の親和性でこのNogo受容体に結合する。従ってこの受容体は抑制シグナルに対する共通の結合蛋白質である可能性が示唆された。Semaphorin受容体の情報伝達の検討:クラス3セマフォリンはNeuropilinとPlexinの複合体を介して成長円錐の退縮反応を引き起こす。LAR型チロシンホスファターゼ(PTPase)が関与する可能性を検討した。LAR型PTPaseに属するLAR,PTPδ,PTPσすべてがSema3A受容体であるNeuropilin-1やPlexin-A1と複合体を形成した。そしてPT...

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コラプシンによる細胞運動抑制とチロシンリン酸化相関の解析

Grant number：11780564 1999 - 2000

日本学術振興会科学研究費助成事業奨励研究(A)

佐々木幸生

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Authorship：Principal investigator Grant type：Competitive

Grant amount：\2200000 （ Direct Cost: \2200000 ）

神経ガイダンス分子セマホリン/コラプシンファミリーの1つ、Sema3Aの情報伝達を解明する目的で、成長円錐退縮応答に対する種々の阻害剤の効果を検討した。その中で、チロシンキナーゼ阻害剤ラベンダスチンAとセリン/トレオニンキナーゼであるcyclin-dependent kinase 5(Cdk5)阻害剤オロモウシンが顕著な阻害効果を示すことを明らかにした。また、Sema3A受容体であるプレキシン-A2(Plex-A2)とニューロピリン-1(NP-1)をCOS-7細胞に発現させたところ、Sema3A刺激により細胞の接着面積が縮小し、球状になることを見出した。この形態変化は、ラベンダスチンAで阻害された。また、Srcファミリーの一員であるfynあるいはcdk5欠損マウスにおいてSema3A応答の減弱を見出した。これらの分子間の関係を免疫沈降で解析したところ、Plex-A2とNP-1複合体にFynが結合し、Plex-A2のチロシンリン酸化を引き起こすことを見出した。さらに、FynはCdk5と結合し、Cdk5のTyr#15のチロシンリン酸化を介して活性化を誘導することが明らかとなった。神経細胞内におけるリン酸化を解析するために、種々のリン酸化特異的抗体を用いて染色したところ、Cdk5のTyr#15リン酸化認識抗体はSema3A投与後成長円錐を一過的に濃染した。同時に、微小管結合タンパク...

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L-DOPA Plays a role as a neurotransmitter regulating blood pressure in the lower brain stem, and endogenously evoked L-DOPA is a casual factor for glutamate release and resultant delayed neuronal cell death by transient ischemia in rats

Grant number：10470026 1998 - 1999

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

GOSHIMA Yoshio, SASAKI Yukio, MIYAMAE Takeaki

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Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid) Grant type：Competitive

Grant amount：\13000000 （ Direct Cost: \13000000 ）

[I] Function of L-DOPA in baroreceptor reflex:[1] (1) Electrolytic lesions of the right nucleus tractus solitarii selectively decrease by 45 % the tissue content of L-DOPA in the dissected ipsilateral caudal ventrolateral medulla.(2) Intermittent stimulation of the right aortic depressor nerve repetitively and constantly causes L-DOPA release, hypotension and bradycardia.(3) Baroreceptor activation selectively evokes L-DOPA. This L-DOPA release is suppressed by acute lesion in the ipsilateral nucleus tractus solitarii.[2] In a single cell neuron isolated from nucleus tractus solitarii, L-DO...

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ドーパはグルタミン酸遊離-神経細胞死の上流因子か? ドーパ新競合的拮抗薬の保護作用

Grant number：10176229 1998

日本学術振興会科学研究費助成事業特定領域研究(A)

三須良實, 古川信也, 宮前丈明, 佐々木幸生, 五嶋良郎

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Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid) Grant type：Competitive

Grant amount：\1600000 （ Direct Cost: \1600000 ）

[1]ラット線条体微量透析ドーパのグルタミン酸遊離:(1)ドーパ1-100nMの用量依存性グルタミン酸遊離増大,(2)6-OHDAi.v.t.処置パーキンソン病モデルにおけるドーパ10nMの同感作作用を再検討したが,確認に至らず,切片でみられた100-300μMドーパの同遊離増大の確認に止まった.(3)6-OHDA内側前脳束投与は,ドパミン(DA)を著減したが,nM用量ドーパのグルタミン酸遊離を確認できず(分担三須).[2]胎仔線条体神経培養系ドーパ自体による神経細胞死:(1)10日培養系における,ドーパ100μMによる立体特異性,NMDA-拮抗薬MK-801,非-NMDA-拮抗薬CNQX-感受性の神経細胞死は,(2)24時間インキュベーション時,Mg^<2+>,TTX添加,Ca^<2+>除去により保護され,ある種伝達物質神経性遊離を示唆しドーパ100-300μMはグルタミン酸を遊離した.(3)同遊離は強力,比較的安定な新競合的ドーパ拮抗薬DOPA cyclohexyl ester(CHE)300μMにより拮抗された(五嶋,佐々木).[3]4血管閉塞脳虚血線条体微量透析系と再交通後病理検索:(1)10分間虚血は,ドーパをDA,グルタミン酸と共に誘発,虚血後10分の各最大遊離は6,220,8倍,各増大は虚血60分後に回復.(2)再交通24時間後,線条体,海馬は神経細胞死を示さず...

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