Updated on 2025/11/10
(BLANK) ( Kyoto University )
微小管
PAR-1
aPKC
上皮細胞
細胞極性
Biochemistry
Pathological Medical Chemistry
細胞運動
細胞接着
Axon initial segment
Golgi apparatus
Life Science / Medical biochemistry
Life Science / Functional biochemistry
Life Science / Cell biology
Kyoto University
1985.4 - 1991.3
Country： Japan
Kyoto University Graduate School, Division of Natural Science
- 1991
Kyoto University Faculty of Science
1981.4 - 1985.3
Country： Japan
Kyoto University Faculty of Science
- 1985
Yokohama City University, Graduate School of Medical Life Science Molecular Cellular Biology Professor
2018.4
Yokohama City University Graduate schol of Medical Life Science Molecular Cellular Biology Laboratory Associate Professor
2013.4 - 2018.3
横浜市立大学 医学群 分子生命医科学系 生命医科学 准教授
2012.4 - 2013.3
横浜市立大学 医学(系)研究科(研究院) 准教授
2004.4 - 2011.3
Yokohama City University Graduate School of Medicine, Graduate
1998.4 - 2004.3
横浜市立大学 医学部 第二生化学教室 助手
1994.4 - 1998.3
国立精神・神経センター、神経研究所 科学技術庁 特別研究員
1991.9 - 1994.3
国立精神・神経センター、神経研究所 流動研究員
1991.4 - 1991.8
Science and Technology Agency, Research fellow
1991 - 1994
National Institute of Neuroscience, NCNP, post doctoral fellow.
1991
日本分子生物学会
日本細胞生物学会
米国細胞生物学会
日本細胞生物学会 代議員
2015.6
Committee type：Academic society
日本細胞生物学会 CSF 常任編集委員
2013.1
Committee type：Academic society
日本細胞生物学会 CSF編集委員
2011.1 - 2012.12
Committee type：Academic society
日本細胞生物学会 評議員
2008.4 - 2015.6
Committee type：Academic society
日本細胞生物学会 プログラム専門委員会 委員
2007.5 - 2010.5
Committee type：Academic society
日本細胞生物学会 将来計画検討委員会 委員
2005.10 - 2007.5
Committee type：Academic society
MTCL2 promotes asymmetric microtubule organization by crosslinking microtubules on the Golgi membrane. International journal
Risa Matsuoka, Masateru Miki, Sonoko Mizuno, Yurina Ito, Chihiro Yamada, Atsushi Suzuki
Journal of cell science 135 ( 11 ) 2022.6
De novo ARF3 variants cause neurodevelopmental disorder with brain abnormality. International journal
Masamune Sakamoto, Kazunori Sasaki, Atsushi Sugie, Yohei Nitta, Tetsuaki Kimura, Semra Gürsoy, Tayfun Cinleti, Mizue Iai, Toru Sengoku, Kazuhiro Ogata, Atsushi Suzuki, Nobuhiko Okamoto, Kazuhiro Iwama, Naomi Tsuchida, Yuri Uchiyama, Eriko Koshimizu, Atsushi Fujita, Kohei Hamanaka, Satoko Miyatake, Takeshi Mizuguchi, Masataka Taguri, Shuuichi Ito, Hidehisa Takahashi, Noriko Miyake, Naomichi Matsumoto
Human molecular genetics 31 ( 1 ) 69 - 81 2021.12
De novo ATP1A3 variants cause polymicrogyria. International journal
Satoko Miyatake, Mitsuhiro Kato, Takuma Kumamoto, Tomonori Hirose, Eriko Koshimizu, Takaaki Matsui, Hideyuki Takeuchi, Hiroshi Doi, Keisuke Hamada, Mitsuko Nakashima, Kazunori Sasaki, Akio Yamashita, Atsushi Takata, Kohei Hamanaka, Mai Satoh, Takabumi Miyama, Yuri Sonoda, Momoko Sasazuki, Hiroyuki Torisu, Toshiro Hara, Yasunari Sakai, Yushi Noguchi, Mazumi Miura, Yoko Nishimura, Kazuyuki Nakamura, Hideyuki Asai, Nodoka Hinokuma, Fuyuki Miya, Tatsuhiko Tsunoda, Masami Togawa, Yukihiro Ikeda, Nobusuke Kimura, Kaoru Amemiya, Asako Horino, Masataka Fukuoka, Hiroko Ikeda, Goni Merhav, Nina Ekhilevitch, Masaki Miura, Takeshi Mizuguchi, Noriko Miyake, Atsushi Suzuki, Shouichi Ohga, Hirotomo Saitsu, Hidehisa Takahashi, Fumiaki Tanaka, Kazuhiro Ogata, Chiaki Ohtaka-Maruyama, Naomichi Matsumoto
Science advances 7 ( 13 ) 2021.3
Phosphorylation and dephosphorylation of Ser852 and Ser889 control the clustering, localization and function of PAR3. International journal
Kazunari Yamashita, Keiko Mizuno, Kana Furukawa, Hiroko Hirose, Natsuki Sakurai, Maki Masuda-Hirata, Yoshiko Amano, Tomonori Hirose, Atsushi Suzuki, Shigeo Ohno
Journal of cell science 133 ( 22 ) 2020.11
SCA21の1家系の臨床的特徴と病理所見
矢彦沢 裕之, 宮武 聡子, 酒井 寿明, 上原 剛, 山田 光則, 羽生 憲直, 二木 保博, 土井 宏, 児矢野 繁, 田中 章景, 鈴木 厚, 松本 直通, 吉田 邦広
臨床神経学 58 ( Suppl. ) S266 - S266 2018.12
A Japanese Family of Spinocerebellar Ataxia Type 21: Clinical and Neuropathological Studies. Reviewed International journal
Hiroyuki Yahikozawa, Satoko Miyatake, Toshiaki Sakai, Takeshi Uehara, Mitsunori Yamada, Norinao Hanyu, Yasuhiro Futatsugi, Hiroshi Doi, Shigeru Koyano, Fumiaki Tanaka, Atsushi Suzuki, Naomichi Matsumoto, Kunihiro Yoshida
Cerebellum (London, England) 17 ( 5 ) 525 - 530 2018.10
Molecular basis of the microtubule-regulating activity of microtubule crosslinking factor 1 Reviewed
Mohammad Abdul Kader, Tomoko Satake, Masatoshi Yoshida, Ikuko Hayashi, Atsushi Suzuki
PLOS ONE 12 ( 8 ) e0182641 2017.8
Regulatory mechanisms and cellular functions of non-centrosomal microtubules. Reviewed International journal
Michiru Nishita, Tomoko Satake, Yasuhiro Minami, Atsushi Suzuki
Journal of biochemistry 162 ( 1 ) 1 - 10 2017.7
MTCL1 plays an essential role in maintaining Purkinje neuron axon initial segment Reviewed
Tomoko Satake, Kazunari Yamashita, Kenji Hayashi, Satoko Miyatake, Miwa Tamura-Nakano, Hiroshi Doi, Yasuhide Furuta, Go Shioi, Eriko Miura, Yukari H. Takeo, Kunihiro Yoshida, Hiroyuki Yahikozawa, Naomichi Matsumoto, Michisuke Yuzaki, Atsushi Suzuki
EMBO JOURNAL 36 ( 9 ) 1227 - 1242 2017.5
Tumor suppressor protein Lgl mediates G1 cell cycle arrest at high cell density by forming an Lgl-VprBP-DDB1 complex Reviewed
Kazunari Yamashita, Mariko Ide, Kana T. Furukawa, Atsushi Suzuki, Hisashi Hirano, Shigeo Ohno
MOLECULAR BIOLOGY OF THE CELL 26 ( 13 ) 2426 - 2438 2015.7
MTCL1 crosslinks and stabilizes non-centrosomal microtubules on the Golgi membrane Reviewed
Yoshinori Sato, Kenji Hayashi, Yoshiko Amano, Mikiko Takahashi, Shigenobu Yonemura, Ikuko Hayashi, Hiroko Hirose, Shigeo Ohno, Atsushi ' Suzuki
NATURE COMMUNICATIONS 5 5266 2014.11
The novel PAR-1-binding protein MTCL1 has crucial roles in organizing microtubules in polarizing epithelial cells Reviewed
Yoshinori Sato, Masashi Akitsu, Yoshiko Amano, Kazunari Yamashita, Mariko Ide, Kyoko Shimada, Akio Yamashita, Hisashi Hirano, Noriaki Arakawa, Takahisa Maki, Ikuko Hayashi, Shigeo Ohno, Atsushi Suzuki
JOURNAL OF CELL SCIENCE 126 ( 20 ) 4671 - 4683 2013.10
Polarity-Dependent Distribution of Angiomotin Localizes Hippo Signaling in Preimplantation Embryos Reviewed
Yoshikazu Hirate, Shino Hirahara, Ken-ichi Inoue, Atsushi Suzuki, Vernadeth B. Alarcon, Kazunori Akimoto, Takaaki Hirai, Takeshi Hara, Makoto Adachi, Kazuhiro Chida, Shigeo Ohno, Yusuke Marikawa, Kazuki Nakao, Akihiko Shimono, Hiroshi Sasaki
CURRENT BIOLOGY 23 ( 13 ) 1181 - 1194 2013.7
aPKC phosphorylates JAM-A at Ser285 to promote cell contact maturation and tight junction formation Reviewed
Sandra Iden, Steve Misselwitz, Swetha S. D. Peddibhotla, Huseyin Tuncay, Daniela Rehder, Volker Gerke, Horst Robenek, Atsushi Suzuki, Klaus Ebnet
JOURNAL OF CELL BIOLOGY 196 ( 5 ) 623 - 639 2012.3
PAR-1/MARK: a Kinase Essential for Maintaining the Dynamic State of Microtubules Reviewed
Kenji Hayashi, Atsushi Suzuki, Shigeo Ohno
CELL STRUCTURE AND FUNCTION 37 ( 1 ) 21 - 25 2012
Maintenance of Dendritic Spine Morphology by Partitioning-Defective 1b through Regulation of Microtubule Growth Reviewed
Kenji Hayashi, Atsushi Suzuki, Syu-ichi Hirai, Yasuyuki Kurihara, Casper C. Hoogenraad, Shigeo Ohno
JOURNAL OF NEUROSCIENCE 31 ( 34 ) 12094 - 12103 2011.8
KIBRA Suppresses Apical Exocytosis through Inhibition of aPKC Kinase Activity in Epithelial Cells Reviewed
Yohei Yoshihama, Kazunori Sasaki, Yosuke Horikoshi, Atsushi Suzuki, Takashi Ohtsuka, Fumihiko Hakuno, Shin-Ichiro Takahashi, Shigeo Ohno, Kazuhiro Chida
CURRENT BIOLOGY 21 ( 8 ) 705 - 711 2011.4
A novel function of the cell polarity-regulating kinase PAR-1/MARK in dendritic spines Reviewed
Kenji Hayashi, Atsushi Suzuki, Shigeo Ohno
BioArchitecture 1 ( 6 ) 261 - 266 2011
The 8th and 9th tandem spectrin-like repeats of utrophin cooperatively form a functional unit to interact with polarity-regulating kinase PAR-1b Reviewed
Kazunari Yamashita, Atsushi Suzuki, Yoshinori Satoh, Mariko Idea, Yoshiko Amano, Maki Masuda-Hirata, Yukiko K. Hayashi, Keisuke Hamada, Kazuhiro Ogata, Shigeo Ohno
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 391 ( 1 ) 812 - 817 2010.1
An essential role of the aPKC-Aurora A-NDEL1 pathway in neurite elongation by modulation of microtubule dynamics Reviewed
Daisuke Mori, Masami Yamada, Yuko Mimori-Kiyosue, Yasuhito Shirai, Atsushi Suzuki, Shigeo Ohno, Hideaki saya, Anthony Wynshaw-Boris, Shinji Hirotsune
NATURE CELL BIOLOGY 11 ( 9 ) 1057 - U47 2009.9
Intracellular polarity protein PAR-1 regulates extracellular laminin assembly by regulating the dystroglycan complex Reviewed
Maki Masuda-Hirata, Atsushi Suzuki, Yoshiko Amano, Kazunari Yamashita, Mariko Ide, Tomoyuki Yamanaka, Michihiro Sakai, Michihiro Imamura, Shigeo Ohno
GENES TO CELLS 14 ( 7 ) 835 - 850 2009.7
Interaction between PAR-3 and the aPKC-PAR-6 complex is indispensable for apical domain development of epithelial cells Reviewed
Yosuke Horikoshi, Atsushi Suzuki, Tomoyuki Yamanaka, Kazunori Sasaki, Keiko Mizuno, Hajime Sawada, Shigenobu Yonemura, Shigeo Ohno
JOURNAL OF CELL SCIENCE 122 ( 10 ) 1595 - 1606 2009.5
aPKC enables development of zonula adherens by antagonizing centripetal contraction of the circumferential actomyosin cables Reviewed
Masaru Kishikawa, Atsushi Suzuki, Shigeo Ohno
JOURNAL OF CELL SCIENCE 121 ( 15 ) 2481 - 2492 2008.8
Regulation of epithelial and endothelial junctions by PAR proteins Reviewed
Klaus Ebnet, Sandra Iden, Volker Gerke, Atsushi Suzuki
FRONTIERS IN BIOSCIENCE-LANDMARK 13 6520 - 6536 2008.5
Affixin activates Rac1 via beta PIX in C2C12 myoblast Reviewed
Chie Matsuda, Kimihiko Kameyama, Atsushi Suzuki, Wataru Mishima, Satoshi Yamaji, Harumasa Okamoto, Ichizo Nishino, Yukiko K. Hayashi
FEBS LETTERS 582 ( 8 ) 1189 - 1196 2008.4
Junction formation induced by polarity proteins, PAR-3 and PAR-6, under low calcium conditions Reviewed
Kishikawa, M., Suzuki, A., Ohno, S.
Yokohama Medical Journal 59 ( 2 ) 125 - 130 2008
Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity Reviewed
Iraj Saadat, Hideaki Higashi, Chikashi Obuse, Mayumi Umeda, Naoko Murata-Kamiya, Yasuhiro Saito, Huaisheng Lu, Naomi Ohnishi, Takeshi Azuma, Atsushi Suzuki, Shigeo Ohno, Masanori Hatakeyama
NATURE 447 ( 7142 ) 330 - U8 2007.5
A distinct PAR complex associates physically with VE-cadherin in vertebrate endothelial cells Reviewed
Sandra Iden, Daniela Rehder, Benjamin August, Atsushi Suzuki, Karen Wolburg-Buchholz, Hartwig Wolburg, Shigeo Ohno, Juergen Behrens, Dietmar Vestweber, Klaus Ebnet
EMBO REPORTS 7 ( 12 ) 1239 - 1246 2006.12
Lgl mediates apical domain disassembly by suppressing the PAR-3-aPKC-PAR-6 complex to orient apical membrane polarity Reviewed
T Yamanaka, Y Horikoshi, N Izumi, A Suzuki, K Mizuno, S Ohno
JOURNAL OF CELL SCIENCE 119 ( 10 ) 2107 - 2118 2006.5
The PAR-aPKC system: lessons in polarity Reviewed
A Suzuki, S Ohno
JOURNAL OF CELL SCIENCE 119 ( 6 ) 979 - 987 2006.3
The gamma-parvin-integrin-linked kinase complex is critically involved in leukocyte-substrate interaction Reviewed
Ryusuke Yoshimi, Satoshi Yamaji, Atsushi Suzuki, Wataru Mishima, Mayumi Okamura, Takashi Obana, Chie Matsuda, Yoshihiro Miwa, Shigeo Ohno, Yoshiaki Ishigatsubo
JOURNAL OF IMMUNOLOGY 176 ( 6 ) 3611 - 3624 2006.3
アフィキシンは,α-アクチンと相互作用し,初期細胞-基質相互作用によって誘発されるF-アクチン再認識のためのインテグリンシグナル伝達に介在する(Affixin interacts with alpha-actinin and mediates integrin signaling for reorganization of F-actin induced by initial cell-substrate interaction)
Yamaji Satoshi, Suzuki Atsushi, Kanamori Heiwa, Mishima Wataru, Yoshimi Ryusuke, Takasaki Hirotaka, Takabayashi Maki, Fujimaki Katsumichi, Fujisawa Shin, Ohno Shigeo, Ishigatsubo Yoshiaki
Cell Structure and Function 30 ( Suppl. ) 112 - 112 2005.6
Dysferlin interacts with affixin (beta-parvin) at the sarcolemma Reviewed
C Matsuda, K Kameyama, K Tagawa, M Ogawa, A Suzuki, S Yamaji, H Okamoto, Nishino, I, YK Hayashi
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY 64 ( 4 ) 334 - 340 2005.4
aPKC acts upstream of PAR-1b in both the establishment and maintenance of mammalian epithelial polarity Reviewed
A Suzuki, M Hirata, K Kamimura, R Maniwa, T Yamanaka, K Mizuno, M Kishikawa, H Hirose, Y Amano, N Izumi, Y Miwa, S Ohno
CURRENT BIOLOGY 14 ( 16 ) 1425 - 1435 2004.8
Affixin interacts with alpha-actinin and mediates integrin signaling for reorganization of F-actin induced by initial cell-substrate interaction Reviewed
S Yamaji, A Suzuki, H Kanamori, W Mishima, R Yoshimi, H Takasaki, M Takabayashi, K Fujimaki, S Fujisawa, S Ohno, Y Ishigatsubo
JOURNAL OF CELL BIOLOGY 165 ( 4 ) 539 - 551 2004.5
The first CH domain of affixin activates Cdc42 and Rac1 through alpha PIX, a Cdc42/Rac1-specific guanine nucleotide exchanging factor Reviewed
W Mishima, A Suzuki, S Yamaji, R Yoshimi, A Ueda, T Kaneko, J Tanaka, Y Miwa, S Ohno, Y Ishigatsubo
GENES TO CELLS 9 ( 3 ) 193 - 204 2004.3
Junctional adhesion molecules (JAMs): more molecules with dual functions? Reviewed
K Ebnet, A Suzuki, S Ohno, D Vestweber
JOURNAL OF CELL SCIENCE 117 ( 1 ) 19 - 29 2004.1
The junctional adhesion molecule (JAM) family members JAM-2 and JAM-3 associate with the cell polarity protein PAR-3: a possible role for JAMs in endothelial cell polarity Reviewed
K Ebnet, M Aurrand-Lions, A Kuhn, F Kiefer, S Butz, K Zander, MKMZ Brickwedde, A Suzuki, BA Imhof, D Vestweber
JOURNAL OF CELL SCIENCE 116 ( 19 ) 3879 - 3891 2003.10
Self-association of PAR-3-mediated by the conserved N-terminal domain contributes to the development of epithelial tight junctions Reviewed
K Mizuno, A Suzuki, T Hirose, K Kitamura, K Kutsuzawa, M Futaki, Y Amano, S Ohno
JOURNAL OF BIOLOGICAL CHEMISTRY 278 ( 33 ) 31240 - 31250 2003.8
Differential induction of protein kinase C isoforms at the cardiac hypertrophy stage and congestive heart failure stage in Dahl salt-sensitive rats Reviewed
Y Koide, K Tamura, A Suzuki, K Kitamura, K Yokoyama, T Hashimoto, N Hirawa, M Kihara, S Ohno, S Umemura
HYPERTENSION RESEARCH 26 ( 5 ) 421 - 426 2003.5
Differential induction of protein kinase C isoforms at the cardiac hypertrophy stage and congestive heart failure stage in Dahl salt-sensitive rats. Reviewed
Koide Y, Tamura K, Suzuki A, Kitamura K, Yokoyama K, Hashimoto T, Hirawa N, Kihara M, Ohno S, Umemura S
Hypertens Res. 26 ( 5 ) 241 - 246 2003.5
Mammalian LgI forms a protein complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity Reviewed
T Yamanaka, Y Horikoshi, Y Sugiyama, C Ishiyama, A Suzuki, T Hirose, A Iwamatsu, A Shinohara, S Ohno
CURRENT BIOLOGY 13 ( 9 ) 734 - 743 2003.4
Protein kinase C lambda/iota (PKC lambda/iota): A PKC isotype essential for the development of multicellular organisms Reviewed
A Suzuki, K Akimoto, S Ohno
JOURNAL OF BIOCHEMISTRY 133 ( 1 ) 9 - 16 2003.1
ILK結合蛋白affixinによるRac1,Cdc42の活性化
三島 渉, 金子 猛, 山路 聡, 吉見 竜介, 三浦 健次, 篠原 岳, 田川 暁大, 山川 泰, 築地 淳, 小松 茂, 西山 晴美, 鈴木 厚, 大野 茂男, 石ヶ坪 良明
アレルギー 52 ( 8 ) 867 - 867 2003
Regulated protein-protein interaction between aPKC and PAR-3 plays an essential role in the polarization of epithelial cells Reviewed
Y Nagai-Tamai, K Mizuno, T Hirose, A Suzuki, S Ohno
GENES TO CELLS 7 ( 11 ) 1161 - 1171 2002.11
Possible role of ILK-affixin complex in integrin-cytoskeleton linkage during platelet aggregation Reviewed
S Yamaji, A Suzuki, H Kanamori, W Mishima, M Takabayashi, K Fujimaki, N Tomita, S Fujisawa, S Ohno, Y Ishigatsubo
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 297 ( 5 ) 1324 - 1331 2002.10
aPKC kinase activity is required for the asymmetric differentiation of the premature junctional complex during epithelial cell polarization Reviewed
A Suzuki, C Ishiyama, K Hashiba, M Shimizu, K Ebnet, S Ohno
JOURNAL OF CELL SCIENCE 115 ( 18 ) 3565 - 3573 2002.9
Involvement of ASIP/PAR-3 in the promotion of epithelial tight junction formation Reviewed
T Hirose, Y Izumi, Y Nagashima, Y Tamai-Nagai, H Kurihara, T Sakai, Y Suzuki, T Yamanaka, A Suzuki, K Mizuno, S Ohno
JOURNAL OF CELL SCIENCE 115 ( 12 ) 2485 - 2495 2002.6
Over-expression of PAR-3 suppresses contact-mediated inhibition of cell migration in MDCK cells Reviewed
A Mishima, A Suzuki, M Enaka, T Hirose, K Mizuno, T Ohnishi, H Mohri, Y Ishigatsubo, S Ohno
GENES TO CELLS 7 ( 6 ) 581 - 596 2002.6
Involvement of protein kinase C in the activation of extracellular signal-regulated kinase 1/2 by UVC irradiation. Reviewed
Zhuang S, Hirai S, Mizuno K, Suzuki A, Akimoto K, Izumi Y, Yamashita A, Ohno S
Biochemical and biophysical research communications 240 ( 2 ) 273 - 278 1997.11
[Protein kinase C in neuronal signaling] Reviewed
Suzuki, A., Ohno, S.
Tanpakushitsu Kakusan Koso 42 ( 3 Suppl ) 1997
Wortmannin inhibits the activation of MAP kinase following vasopressin V1 receptor stimulation Reviewed
N Nishioka, S Hirai, K Mizuno, S Osada, A Suzuki, K Kosaka, S Ohno
FEBS LETTERS 377 ( 3 ) 393 - 398 1995.12
MOLECULAR-ORGANIZATION AT THE GLYCOPROTEIN-COMPLEX-BINDING SITE OF DYSTROPHIN - 3 DYSTROPHIN-ASSOCIATED PROTEINS BIND DIRECTLY TO THE CARBOXY-TERMINAL PORTION OF DYSTROPHIN Reviewed
A SUZUKI, M YOSHIDA, K HAYASHI, Y MIZUNO, Y HAGIWARA, E OZAWA
EUROPEAN JOURNAL OF BIOCHEMISTRY 220 ( 2 ) 283 - 292 1994.3
Cell Polarity: Biological Role and Basic Mechanisms
SUZUKI Atsushi（ Role： ContributorChapter 2, 25-50）
Springer International Publishing AG 2015
Defects in muscle-cytoskeleton interaction in diseased states, in Treatise on the Cytoskeleton(Hesketh, J. E. & Pryme, I. F. , eds)
Treatise on the Cytoskeleton 1993
普遍的細胞極性制御システム：PAR-aPKCシステムの作用機構 Invited
鈴木 厚
生体の科学 63 ( 3 ) 189 - 195 2012.6
Maintenance of Dendritic Spine Morphology by PAR1b through Regulation of Microtubule Growth.
K. Hayashi, A. Suzuki, C. C. Hoogenraad, S. Ohno
MOLECULAR BIOLOGY OF THE CELL 22 2011
細胞極性遺伝子:マウスモデルから疾患の理解と診断・治療・予防へ
大野茂男, 廣瀬智威, 秋本和憲, 山下暁朗, 鈴木厚, 平井秀一
横浜医学 60 ( 1/2 ) 84 - 90 2009.5
PAR‐3とaPKC‐PAR‐6との相互作用は,上皮細胞のアピカルドメインの形成に必要である。
堀越洋輔, 鈴木厚, 山中智行, 佐々木和教, 水野恵子, 米村重信, 大野茂男
レーザ顕微鏡研究会講演会抄録集 35th 47 - 50 2009
筋ジストロフィーおよびその関連する疾患の病態生理の解明と治療薬物の開発に関する研究 VI.各種蛋白質の発現と機能 細胞極性制御タンパク質キナーゼ,PAR‐1によるUtrophin/Dystroglycanの機能制御機構の解明
鈴木厚, 山下和成, 大野茂男, 今村道博, 林由起子
筋ジストロフィーおよびその関連する疾患の病態生理の解明と治療薬物の開発に関する研究 清水班 平成17-19年度研究報告書 83 2008
Affixin activates Rac1 via PIX in C2C12 myoblasts
C. Matsuda, K. Kameyarna, A. Suzuki, W. Mishima, S. Yamaji, H. Okamoto, I. Nishino, Y. Hayashi
NEUROMUSCULAR DISORDERS 17 ( 9-10 ) 790 - 790 2007.10
The integrin-linked kinase-gamma-parvin complex is involved in Integrin-Dependent leukocyte adhesion and spreading.
Ryusuke Yoshimi, Toshi Yamaji, Atsushi Suzuki, Wataru Mishima, Mayumi Okamura, Takashi Obana, Yoshiaki Ishigatsubo
ARTHRITIS AND RHEUMATISM 54 ( 9 ) S578 - S578 2006.9
Dysferlin interacts with affixin (beta-parvin) at the sarcolemma
Chie Matsuda, Kimihiko Kameyama, Kazuhiko Tagawa, Megumu Ogawa, Atsushi Suzuki, Satoshi Yamaji, Harumasa Okamoto, Ichizo Nishino, Yukiko Hayashi
NEUROMUSCULAR DISORDERS 16 S93 - S93 2006.7
自己免疫疾患とシグナル伝達 γ-parvinはβ1 integrinのaffinityを変化させることにより白血球-基質間接着に関与する
吉見 竜介, 山路 聡, 鈴木 厚, 三島 渉, 岡村 真由美, 尾鼻 孝滋, 桐野 洋平, 関口 章子, 小林 弘, 井畑 淳, 泉二 恭輔, 上田 敦久, 岳野 光洋, 石ヶ坪 良明
日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集 50回・15回 154 - 154 2006.3
PAR‐3は,上皮細胞のアピカルドメインの形成に必要である。
堀越洋輔, 山中智行, 泉奈津子, 水野恵子, 鈴木厚, 大野茂男
日本分子生物学会年会講演要旨集 28th 632 2005.11
The first CH domain of affixin activates Cdc42 and Rac1 through alphaPIX, a Cdc42/Rac1-specific guanine nucleotide exchanging factor
Wataru Mishima, Atsushi Suzuki, Satoshi Yamaji, Ryusuke Yoshimi, Mayumi Okamura, Shigeo Ohno, Yoshiaki Ishigatsubo
CELL STRUCTURE AND FUNCTION 30 53 - 53 2005.6
gamma-Parvin plays an important role in integrin-dependent leukocyte migration
Ryusuke Yoshimi, Satoshi Yamaji, Atsushi Suzuki, Mayumi Okamura, Wataru Mishima, Shigeo Ohno, Yoshiaki Ishigatsubo
CELL STRUCTURE AND FUNCTION 30 111 - 111 2005.6
Integrin-linked kinase(ILK),γ-parvin系によるインテグリン媒介性白血球遊走の制御
吉見 竜介, 山路 聡, 鈴木 厚, 岡村 真由美, 三島 渉, 上田 敦久, 岳野 光洋, 石ヶ坪 良明
日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集 49回・14回 161 - 161 2005.4
aPKC/PARシステム：多細胞生物の細胞極性を普遍的にコントロールする分子制御装置 Invited
鈴木 厚
細胞工学 24 ( 3 ) 227 - 230 2005
ほ乳類上皮細胞の極性制御におけるPAR‐3複合体,Lethal giant larvae複合体の機能解析
山中智行, 堀越洋輔, 泉奈津子, 鈴木厚, 村松玲子, 三輪佳宏, 大野茂男
日本分子生物学会年会プログラム・講演要旨集 27th 607 2004.11
Effect of aPKC inhibition on highly-integrated reorganaization of F-actin triggered by initial cell-cell contacts of epithelial cells
Masaru Kishikawa, Atsushi Suzuki, Shigeo Ohno
CELL STRUCTURE AND FUNCTION 29 47 - 47 2004.5
The junctional adhesion molecule (JAM) family members JAM-2 and JAM-3 associate with the cell polarity protein PAR-3: a possible role for JAMs in endothelial cell polarity
K Ebnet, M Aurrand-Lions, A Kuhn, F Kiefer, S Butz, K Zander, MKMZ Brickwedde, A Suzuki, BA Imhof, D Vestweber
JOURNAL OF CELL SCIENCE 116 ( 19 ) 3879 - 3891 2003.10
Self-association of PAR-3-mediated by the conserved N-terminal domain contributes to the development of epithelial tight junctions
K Mizuno, A Suzuki, T Hirose, K Kitamura, K Kutsuzawa, M Futaki, Y Amano, S Ohno
JOURNAL OF BIOLOGICAL CHEMISTRY 278 ( 33 ) 31240 - 31250 2003.8
Mammalian LgI forms a protein complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity
T Yamanaka, Y Horikoshi, Y Sugiyama, C Ishiyama, A Suzuki, T Hirose, A Iwamatsu, A Shinohara, S Ohno
CURRENT BIOLOGY 13 ( 9 ) 734 - 743 2003.4
Protein kinase C lambda/zeta: A PKC isoform essential for the development or multicellular organisms
J. Biochem. 133: 9-16 2003
細胞極性制御の分子機構
細胞 35号 No.13 542-545 2003
Possible role of ILK-affixin complex in integrin-cytoskeleton linkage during platelet aggregation
S Yamaji, A Suzuki, H Kanamori, W Mishima, M Takabayashi, K Fujimaki, N Tomita, S Fujisawa, S Ohno, Y Ishigatsubo
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 297 ( 5 ) 1324 - 1331 2002.10
aPKC kinase activity is required for the asymmetric differentiation of the premature junctional complex during epithelial cell polarization
A Suzuki, C Ishiyama, K Hashiba, M Shimizu, K Ebnet, S Ohno
JOURNAL OF CELL SCIENCE 115 ( 18 ) 3565 - 3573 2002.9
Over-expression of PAR-3 suppresses contact-mediated inhibition of cell migration in MDCK cells
A Mishima, A Suzuki, M Enaka, T Hirose, K Mizuno, T Ohnishi, H Mohri, Y Ishigatsubo, S Ohno
GENES TO CELLS 7 ( 6 ) 581 - 596 2002.6
Involvement of ASIP/PAR-3 in the promotion of epithelial tight junction formation
T Hirose, Y Izumi, Y Nagashima, Y Tamai-Nagai, H Kurihara, T Sakai, Y Suzuki, T Yamanaka, A Suzuki, K Mizuno, S Ohno
JOURNAL OF CELL SCIENCE 115 ( 12 ) 2485 - 2495 2002.6
A possible involvement of atypical PKC signaling pathway in cardiac hypertrophy
Y Koide, K Tamura, A Suzuki, M Nakayama, K Kitamura, K Akimoto, S Ohno, S Umemura
JOURNAL OF HYPERTENSION 20 S114 - S114 2002.6
Regulated protien-protein interaction between aPKC and PAR-3 plays an essential role in th epolarization of epithelial cells.
Genes to Cells 7, 1161-1171 2002
プロテインキナーゼCの生理的機能の解明にむけた研究戦略
実験医学 20:161-167 2002
aPKC functions to develop the primordial junctional complexes into the epithelia-specific asymmetric junctional structures
A Suzuki, C Ishiyama, K Ebnet, Y Takai, S Ohno
MOLECULAR BIOLOGY OF THE CELL 12 112A - 112A 2001.11
Dynamic changes in protein components of the tight junction during liver regeneration
Y Takaki, S Hirai, N Manabe, Y Izumi, T Hirose, M Nakaya, A Suzuki, K Mizuno, K Akimoto, S Tsukita, T Shuin, S Ohno
CELL AND TISSUE RESEARCH 305 ( 3 ) 399 - 409 2001.9
PAR-6 regulates aPKC activity in a novel way and mediates cell-cell contact-induced formation of the epithelial junctional complex
T Yamanaka, Y Horikoshi, A Suzuki, Y Sugiyama, K Kitamura, R Maniwa, Y Nagai, A Yamashita, T Hirose, H Ishikawa, S Ohno
GENES TO CELLS 6 ( 8 ) 721 - 731 2001.8
The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM)
K Ebnet, A Suzuki, Y Horikoshi, T Hirose, MK Meyer zu Brickwedde, S Ohno, D Vestweber
EMBO JOURNAL 20 ( 14 ) 3738 - 3748 2001.7
A novel integrin-linked kinase-binding protein, affixin, is involved in the early stage of cell-substrate interaction
S Yamaji, A Suzuki, Y Sugiyama, Y Koide, M Yoshida, H Kanamori, H Mohri, S Ohno, Y Ishigatsubo
JOURNAL OF CELL BIOLOGY 153 ( 6 ) 1251 - 1264 2001.6
Atypical protein kinase C is involved in the evolutionarily conserved PAR protein complex and plays a critical role in establishing epithelia-specific junctional structures
A Suzuki, T Yamanaka, T Hirose, N Manabe, K Mizuno, M Shimizu, K Akimoto, Y Izumi, T Ohnishi, S Ohno
JOURNAL OF CELL BIOLOGY 152 ( 6 ) 1183 - 1196 2001.3
堀越洋輔, 山中智行, 鈴木厚, 大野茂男
日本分子生物学会年会プログラム・講演要旨集 23rd 681 2000.11
MAPK upstream kinase (MUK)-binding inhibitory protein, a negative regulator of MUK/dual leucine zipper-bearing kinase/leucine zipper protein kinase
K Fukuyama, M Yoshida, A Yamashita, T Deyama, M Baba, A Suzuki, H Mohri, Z Ikezawa, H Nakajima, S Hirai, S Ohno
JOURNAL OF BIOLOGICAL CHEMISTRY 275 ( 28 ) 21247 - 21254 2000.7
Muscle develops a specific form of small heat shock protein complex composed of MKBP/HSPB2 and HSPB3 during myogenic differentiation
Y Sugiyama, A Suzuki, M Kishikawa, R Akutsu, T Hirose, MMY Waye, SKW Tsui, S Yoshida, S Ohno
JOURNAL OF BIOLOGICAL CHEMISTRY 275 ( 2 ) 1095 - 1104 2000.1
哺乳動物上皮細胞の極性形成におけるaPKCの役割
細胞工学 19 1763 - 1768 2000
鈴木 厚, 大野 茂男
生体の科学 51 ( 2 ) 96 - 102 2000
The small heat shock-related protein, HSP20, is phosphorylated on serine 16 during cyclic nucleotide-dependent relaxation
A Beall, D Bagwell, D Woodrum, TA Stoming, K Kato, A Suzuki, H Rasmussen, CM Brophy
JOURNAL OF BIOLOGICAL CHEMISTRY 274 ( 39 ) 28058 - 28058 1999.9
Translocation of HSP27 and MKBP in ischemic heart
K Yoshida, T Aki, K Harada, KMA Shama, Y Kamoda, A Suzuki, S Ohno
CELL STRUCTURE AND FUNCTION 24 ( 4 ) 181 - 185 1999.8
The small heat shock-related protein, HSP20, is phosphorylated on serine 16 during cyclic nucleotide-dependent relaxation
A Beall, D Bagwell, D Woodrum, TA Stoming, K Kato, A Suzuki, H Rasmussen, CM Brophy
JOURNAL OF BIOLOGICAL CHEMISTRY 274 ( 16 ) 11344 - 11351 1999.4
Transient up-regulation of myotonic dystrophy protein kinase-binding protein, MKBP, and HSP27 in the neonatal myocardium
KM Abu Shama, A Suzuki, K Harada, N Fujitani, H Kimura, S Ohno, K Yoshida
CELL STRUCTURE AND FUNCTION 24 ( 1 ) 1 - 4 1999.2
A muscle-specific stress-responsible system which is composed of diversed members of the small heat shock protein family
SUGIYAMA Y., SUZUKI A., KISHIKAWA M., AKUTSU R., HIROSE T., KATO K., WAYE M., OHNO S.
21 578 - 578 1998.12
Structure and function of MUK(an upstreame factor of JNK pathway)regulatory protein
FUKUYAMA K., YOSHIDA M., YAMASHITA A., SUZUKI A., HIRAI S., NAKAJIMA H., OHNO S.
21 551 - 551 1998.12
Possible involvement of the ASIP-aPKC system in biogenesis of the cell-cell junctional complexes
SUZUKI A., OHNISHI T., IZUMI Y., HIROSE T., NODA K., OHNO S.
21 551 - 551 1998.12
aPKC群結合タンパク質の単離およびその生化学的解析
田中純平, 秋本和憲, 山中智行, 中谷雅明, 吉田道彦, 広瀬智威, 鈴木厚, 田沼靖一, 大野茂男
日本分子生物学会年会プログラム・講演要旨集 21st 550 1998.11
MKBP, a novel member of the small heat shock protein family, binds and activates the myotonic dystrophy protein kinase
A Suzuki, Y Sugiyama, Y Hayashi, N Nyu-i, M Yoshida, Nonaka, I, S Ishiura, K Arahata, S Ohno
JOURNAL OF CELL BIOLOGY 140 ( 5 ) 1113 - 1124 1998.3
YSK1, a novel mammalian protein kinase structurally related to Ste20 and SPS1, but is not involved in the known MAPK pathways
S Osada, M Izawa, R Saito, K Mizuno, A Suzuki, S Hirai, S Ohno
ONCOGENE 14 ( 17 ) 2047 - 2057 1997.5
脳・神経機能とプロテインキナーゼC
蛋白質核酸酵素 42 ( 3 ) 411 1997
PKCδはRasを介さずRafを介してMAPキナーゼ経路を活性化する
植田 吉彦, 長田 真一, 平井 秀一, 水野 恵子, 鈴木 厚, 大野 茂男
日本分子生物学会年会プログラム・講演要旨集 19 614 - 614 1996.8
筋緊張性ジストロフィー責任タンパク質, Myotonine protein kinaseに結合する新規small heat shock protein, MKBP
鈴木 厚, 吉田 道彦, 乳井 伸夫, 石浦 章一, 鈴木 紘一, 大野 茂男
日本分子生物学会年会プログラム・講演要旨集 19 696 - 696 1996.8
PKCとその新規結合蛋白質D1-5Aの相互作用の解析
玉井 陽子, 泉 裕士, 平井 秀一, 水野 恵子, 鈴木 厚, 山田 道之, 大野 茂男
日本分子生物学会年会プログラム・講演要旨集 19 614 - 614 1996.8
Protein Kinase C(PKC)のMARCKSに対するフォスファチジルセリン依存的・非依存的結合
松岡 有理子, 泉 裕士, 玉井 陽子, 中岡 隆志, 辻 崇一, 平井 秀一, 水野 恵子, 鈴木 厚, 中嶋 弘, 大野 茂男
日本分子生物学会年会プログラム・講演要旨集 19 615 - 615 1996.8
Polymorphism of F-actin assembly .2. Effects of barbed end capping on F-actin assembly
A Suzuki, T Ito
BIOCHEMISTRY 35 ( 16 ) 5245 - 5249 1996.4
Polymorphism of F-actin assembly .1. A quantitative phase diagram of F-actin
A Suzuki, M Yamazaki, T Ito
BIOCHEMISTRY 35 ( 16 ) 5238 - 5244 1996.4
Protein kinase C δ activates the MEK-ERK pathway in a manner independent of Ras and dependent on Raf
Yoshihiko Ueda, Syu-Ichi Hirai, Shin-Ichi Osada, Atsushi Suzuki, Keiko Mizuno, Shigeo Ohno
Journal of Biological Chemistry 271 ( 38 ) 23512 - 23519 1996
MAMMALIAN ALPHA-1-SYNTROPHIN AND BETA-1-SYNTROPHIN BIND TO THE ALTERNATIVE SPLICE-PRONE REGION OF THE DYSTROPHIN COOH TERMINUS
A SUZUKI, M YOSHIDA, E OZAWA
JOURNAL OF CELL BIOLOGY 128 ( 3 ) 373 - 381 1995.2
DIFFERENT MODE OF AP1/JUN ACTIVATION BY RAS AND PKC-DELTA
SI HIRAI, Y IZUMI, Y TAMAI, S OSADA, K MIZUNO, A SUZUKI, S OHNO
JOURNAL OF CELLULAR BIOCHEMISTRY 35 - 35 1995.1
DYSTROPHIN-ASSOCIATED PROTEINS IN MUSCULAR-DYSTROPHY
E OZAWA, M YOSHIDA, A SUZUKI, Y MIZUNO, Y HAGIWARA, S NOGUCHI
HUMAN MOLECULAR GENETICS 4 1711 - 1716 1995
プロテインキナーゼC ファミリー
生体の科学 46 ( 5 ) 592 1995
SELECTIVE DEFECT OF SARCOGLYCAN COMPLEX IN SEVERE CHILDHOOD AUTOSOMAL RECESSIVE MUSCULAR-DYSTROPHY MUSCLE
Y MIZUNO, S NOGUCHI, H YAMAMOTO, M YOSHIDA, A SUZUKI, Y HAGIWARA, YK HAYASHI, K ARAHATA, NONAKA, I, S HIRAI, E OZAWA
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 203 ( 2 ) 979 - 983 1994.9
DISSOCIATION OF THE COMPLEX OF DYSTROPHIN AND ITS ASSOCIATED PROTEINS INTO SEVERAL UNIQUE GROUPS BY N-OCTYL BETA-D-GLUCOSIDE
M YOSHIDA, A SUZUKI, H YAMAMOTO, S NOGUCHI, Y MIZUNO, E OZAWA
EUROPEAN JOURNAL OF BIOCHEMISTRY 222 ( 3 ) 1055 - 1061 1994.6
Activation of nPKC through PI3K.
守屋繁春, 秋本和憲, 長田真一, 鈴木厚, 水野恵子, 平井秀一, 井口泰泉, KAZLAUSKAS A, 大野茂男
日本分子生物学会年会プログラム・講演要旨集 17th 1994
Molecular organization at the glycoprotein-binding site of dystrophin(I)-Three dystrophin-associated protein, 43DAG(A3a), A0 and β-A1, directly bind to the carboxy-terminal portion of dystrophin-
European Journal of Biochemistry 220,283- 1993
PROTEINASE-SENSITIVE SITES ON ISOLATED RABBIT DYSTROPHIN
M YOSHIDA, A SUZUKI, T SHIMIZU, E OZAWA
JOURNAL OF BIOCHEMISTRY 112 ( 4 ) 433 - 439 1992.10
GLYCOPROTEIN-BINDING SITE OF DYSTROPHIN IS CONFINED TO THE CYSTEINE-RICH DOMAIN AND THE 1ST-HALF OF THE CARBOXY-TERMINAL DOMAIN
A SUZUKI, M YOSHIDA, H YAMAMOTO, E OZAWA
FEBS LETTERS 308 ( 2 ) 154 - 160 1992.8
REGULATION OF WATER-FLOW BY ACTIN-BINDING PROTEIN-INDUCED ACTIN GELATION
T ITO, A SUZUKI, TP STOSSEL
BIOPHYSICAL JOURNAL 61 ( 5 ) 1301 - 1305 1992.5
FORMATION OF LIQUID-CRYSTALLINE PHASE OF ACTIN FILAMENT SOLUTIONS AND ITS DEPENDENCE ON FILAMENT LENGTH AS STUDIED BY OPTICAL BIREFRINGENCE
A SUZUKI, T MAEDA, T ITO
BIOPHYSICAL JOURNAL 59 ( 1 ) 25 - 30 1991.1
OSMOELASTIC COUPLING IN BIOLOGICAL STRUCTURES - FORMATION OF PARALLEL BUNDLES OF ACTIN-FILAMENTS IN A CRYSTALLINE-LIKE STRUCTURE CAUSED BY OSMOTIC-STRESS
A SUZUKI, M YAMAZAKI, T ITO
BIOCHEMISTRY 28 ( 15 ) 6513 - 6518 1989.7
POLYMORPHISM OF ACTIN FILAMENT ASSEMBLY AND ITS PHYSIOLOGICAL FUNCTIONS - OSMOTIC RESPONSE OF NON-MUSCLE CELL
T ITO, A SUZUKI, M YAMAZAKI, S OHNISHI
CELL STRUCTURE AND FUNCTION 12 ( 6 ) 620 - 620 1987.12
The Naito Foundation reserch grant
2016.3 The Naito Foundation
SUZUKI Atsushi
医学会賞
2004 横浜市立大学 医学会
鈴木 厚
最優秀発表賞
1992 国立精神神経センター、神経研究所
鈴木 厚
Investigation of MTCL proteins which regulate assembly structures of microtubules based on the Golgi membrane.
Grant number：22H02621 2022.4 - 2025.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B) Grant-in-Aid for Scientific Research (B)
Grant amount：\17420000 （ Direct Cost: \13400000 、 Indirect Cost：\4020000 ）
Study on MTCL proteins, which organize microtubule assembly structures based on the Golgi membrane.
Grant number：23K23884 2022.4 - 2025.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
Grant amount：\17420000 （ Direct Cost: \13400000 、 Indirect Cost：\4020000 ）
Study on the regulatory mechanisms of microtubule organization by MTCL proteins.
Grant number：19H03228 2019.4 - 2022.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
Atsushi Suzuki
Grant amount：\17420000 （ Direct Cost: \13400000 、 Indirect Cost：\4020000 ）
We have previously found the coiled-coil protein MTCL1, which stabilizes microtubules nucleated from the Golgi membrane. In this study, we newly analyzed an MTCL1 paralog, MTCL2, which preferentially acts on the perinuclear microtubules accumulated around the Golgi. MTCL2 associates with the Golgi membrane through the N-terminal coiled-coil region and directly binds microtubules through the conserved C-terminal domain without promoting microtubule stabilization. Knockdown of MTCL2 significantly impaired microtubule accumulation around the Golgi as well as the compactness of the Golgi ribbon assembly structure. Together with several additional results, we concluded that MTCL2 promotes asymmetric microtubule organization by crosslinking microtubules on the Golgi membrane. We also suggested that this function of MTCL2 enables integration of the centrosomal and Golgi-associated microtubules on the Golgi membrane, supporting directional migration.
Study of crosslinked and stabilized microtubules
Grant number：16H04765 2016.4 - 2019.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B) Grant-in-Aid for Scientific Research (B)
Suzuki Atsushi, OKADA Yasushi, SATAKE Tomoko
Authorship：Principal investigator Grant type：Competitive
Grant amount：\17550000 （ Direct Cost: \13500000 、 Indirect Cost：\4050000 ）
Microtubule is the essential cytoskeletal filament indispensable for cell polarity establishment. In this study, we have studied the molecular mechanisms by which microtubules are stabilized and crosslinked, and the physiological significance of such microtubule regulations. We have obtained the following results about the novel microtubule-regulating protein, MTCL1, which we had found previously. ① the N-terminal region of MTCL1 crosslinks dynamic microtubule flexibly. ② the C-terminal region of MTCL1 stabilizes microtubules by inducing the GTP-bound form of tubulin within the filament. ③ through these activities, MTCL1 plays essential roles for the development of axon initial segment and axonal polarity of cerebellar Purkinje neurons.
微小管制御異常に起因する脊髄小脳変性症の新たな発症メカニズムの解明
2015.9 - 2017.3
内藤記念科学振興財団 内藤記念科学研究助成
鈴木 厚
Authorship：Principal investigator Grant type：Competitive
MTCL1 plays an essential role to maintain axon initial segment
Grant number：15K15069 2015.4 - 2017.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research Grant-in-Aid for Challenging Exploratory Research
SUZUKI Atsushi, SATAKE Tomoko, MIYATAKE Satoko
Authorship：Principal investigator Grant type：Competitive
Grant amount：\3640000 （ Direct Cost: \2800000 、 Indirect Cost：\840000 ）
The axon initial segment (AIS) is a specialized domain essential for neuronal function, the formation of which begins with localization of an Ankyrin-G (AnkG) scaffold. However, the mechanism directing and maintaining AnkG localization is largely unknown. In this study, we demonstrate that in vivo knockdown of MTCL1 in cerebellar Purkinje cells causes loss of axonal polarity coupled with AnkG mislocalization. MTCL1 lacking MT-stabilizing activity failed to restore these defects. Interestingly, during postnatal AIS development, colocalization of MTCL1 with these stable MT bundles was transiently observed in the axon hillock and proximal axon. These results indicate that MTCL1-mediated formation of stable MT bundles is crucial for AnkG localization. We also demonstrate that Mtcl1-gene disruption results in abnormal motor coordination with Purkinje cell degeneration, and provide evidence suggesting possible involvement of MTCL1 dysfunction in the pathogenesis of spinocerebellar ataxia.
Molecular mechanisms of the polarity-regulating signaling
Grant number：22247030 2010 - 2012
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
OHNO Shigeo, HIRAI Syu-ichi, SUZUKI Atsushi, AKIMOTO Kazunori, YAMASHITA Akio, HIROSE Tomonori, NAKAYA Masa-aki, SASAKI Kazunori
Grant amount：\44460000 （ Direct Cost: \34200000 、 Indirect Cost：\10260000 ）
To understand the molecular mechanism of the PAR-aPKC polarity complex to regulate cell polarity, we identified ASPP2 as a novel member of the PAR-aPKC polarity complex. ASPP2 as well as PAR3 localizes to the apical junctional complex of epithelial cells and their localization are mutually-dependent.Another finding involves a novel regulatory system for the exocytosis of apical membrane proteins by the PAR-aPKC polarity complex. We identified KIBRA as a competitive inhibitor of aPKC kinase activity. Further studies revealed that KIBRA suppress apical exocytosis through inhibition of the aPKC kinase activity.
Grant number：21116004 2009 - 2012
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
SUZUKI Atsushi, HIROSE Tomonori, NAKAYA Masaaki
Authorship：Principal investigator Grant type：Competitive
Grant amount：\128700000 （ Direct Cost: \99000000 、 Indirect Cost：\29700000 ）
In the very early stages of the mammalian embryogenesis (8 to 32 cells), the establishment of epithelial polarity in the outer cells of the cell mass is crucially important to guarantee the gradual fixation of the fates of the individual cells. Based on the fact that dynamic change of the epithelial cell polarity is crucially important for the mammalian embryonic development, in this research project, we have intensively analyzed the mechanisms by which the evolutionarily-conserved cell polarity-regulating proteins, the PAR-aPKC proteins, control the epithelial polarity. As a result, we succeeded to reveal three kinds of the novel molecular mechanisms, and provided the important insights and basis for the future research on the early embryogenesis of mammals.
Cell Community in early mammalian development
Grant number：21116001 2009 - 2012
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
FUJIMORI Toshihiko, SASAKI Hiroshi, MENO Chikara, SUZUKI Atsushi, KOBAYASHI Tetsuya
Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid) Grant type：Competitive
Grant amount：\29640000 （ Direct Cost: \22800000 、 Indirect Cost：\6840000 ）
Grant number：20570186 2008 - 2010
Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research(基盤研究(C)) 基盤研究(C)
Atsushi SUZUKI
Authorship：Principal investigator Grant type：Competitive
Grant amount：\4940000 （ Direct Cost: \3800000 、 Indirect Cost：\1140000 ）
Epithelial cells cover the boundary between our body and external environment, and thus develop functional asymmetry (polarity) between the cell membranes facing internal and external environment. It has been demonstrated that abnormal epithelial polarity leads to physiological deficiency. In this study, we have analyzed how the general cell polarity-regulating protein, PAR-1, plays important roles for epithelial polarity, especially by analyzing its binding proteins.
Grant number：18570183 2006 - 2007
Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research(基盤研究(C)) 基盤研究(C)
Atsushi SUZUKI
Authorship：Principal investigator Grant type：Competitive
Grant amount：\4110000 （ Direct Cost: \3600000 、 Indirect Cost：\510000 ）
The PAR-aPKC system plays crucial roles in establishing the apicobasal polarity of epithelial cells. On the other hand, the importance of extracellular matrix (ECM) components, especially laminin, in determining the orientation of the epithelial polarity axis has recently been established. However, molecular links between the PAR-aPKC system and ECM are still missing. In this work, we revealed that one component of the PAR-aPKC system, PAR-lb kinase, regulates extracellular laminin organization by controlling the localization and function of the laminin receptor complex, i.e. the utrophin-d...
The role of CRMP family proteins in the establishment of neural tissue architectures
Grant number：17082006 2005 - 2009
Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research(特定領域研究) 特定領域研究
Yoshio GOSHIMA, 鈴木 厚, 中村 史雄, Toshio OOSHIMA, 内田 穣
Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid) Grant type：Competitive
Grant amount：\101700000 （ Direct Cost: \101700000 ）
In developing brain, axon and dendritic guidance are regulated by repulsive and attractive axon guidance molecules such as semaphorin3A (Sema3A) and netrin. Collpapsin response mediator protein (CRMP) has originally been identified as an intracellular protein that mediates Sema3A. We found that Sema3A elicits axoplasmic transport that may be involved in regulating the localization of AMPA type glutamate receptors in hippocampal neurons. To elucidate in vivo role of CRMPs, we generated several crmp1 and other crmp family gene-deficient mice and performed phenotypic analysis of these mice. Fo...
Cell Polarity Signaling and Cancer
Grant number：17014076 2005 - 2009
Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research(特定領域研究) 特定領域研究
Shigeo OHNO, 水野 恵子, Atsushi SUZUKI, Kazunori AKIMOTO, Tomonori HIROSE, Keiko MIZUNO
Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid) Grant type：Competitive
Grant amount：\328800000 （ Direct Cost: \328800000 ）
A series of experiments focusing on the aPKC-PAR complex revealed (1) the new role of PAR1 on the recruitment and organization of extracellular laminin through utrophin/dystroglucan complex. We have also identified ASPP2, known as a mediator of apoptic function of p53, as a partner of the aPKC-PAR complex. (2) In mammary epithelial stem/progenitor cells the aPKC-ErbB2 pathway negatively regulates proliferation. (3) Relationships between aPKC overexpression and the recurrence of prostate cancer, metastasis of stomach cancer, and grade of mammary cancer. Intensive studies on prostate cancer c...
Molecular mechanism of mammalian mRNA surveillance
Grant number：17209010 2005 - 2006
Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research(基盤研究(A)) 基盤研究(A)
Shigeo OHNO, 平井 秀一, 鈴木 厚, 水野 恵子, 秋本 和憲
Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid) Grant type：Competitive
Grant amount：\51350000 （ Direct Cost: \39500000 、 Indirect Cost：\11850000 ）
Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that degrades mRNA containing premature termination codons (PTCs). In mammalian cells, recognition of PTCs requires translation and depends on the presence on the mRNA with the splicing-dependent exon junction complex (EJC). While it is known that a key event in the triggering of NMD is phosphorylation of the trans-acting factor, Upf1, by SMG-1, the relationship between Upf1 phosphorylation and PTC recognition remains undetermined. Here we show that SMG-1 binds to the mRNA-associated components of the EJC, Upf2, Upf3b, elF4A3, M...
Grant number：16044239 2004 - 2005
文部科学省 科学研究費補助金(特定領域研究) 特定領域研究
鈴木 厚
Authorship：Principal investigator Grant type：Competitive
Grant amount：\5400000 （ Direct Cost: \5400000 ）
昨年度の成果に基づき、今年度は主として以下の二点について研究を進めた。1)aPKC-PARシステムに属する上皮細胞のバソラテラル面に局在するセリン・スレオニンキナーゼ、PAR-1bがutrophin/dystroglycan(以下、Utr/DG)複合体と結合していることを発見した。このUtr/DG複合体は、上皮細胞において細胞外の基底膜主成分ラミニンと細胞内アクチン骨格系を結びつける働きをしている。今回、PAR-1bがこのUtr/DG複合体のバソラテラル面への局在に必須な役割をしていること、およびそのことを介して、細胞外ラミニンのオーガナイズに働いていることを明らかとした。昨年度、PAR-1bは上皮細胞のアピカル膜ドメインの発達に必須であることを示したが、この活性がPAR-1bによるUtr/DGを介した細胞外ラミニンの制御に起因することも確認した。これらの結果は、ともに上皮極性、および上皮細胞内の選択的輸送に重要な寄与をしている、細胞内極性タンパク質と細胞外基質タンパク質の機能的連関を始めて示した結果である。PAR-1bがいかにしてUtr/DGの局在を制御するのかは現在解析中であるが、膜タンパク質であるDGをPAR-1bがリン酸化し小胞輸送を介したDGの取り込みをPAR-1bが制御している可能性が示唆されつつある。2)aPKC-PARシステムと相互作用することで上皮極性を制御...
Molecular mechanism of mammalian mRNA surveillance
Grant number：15209013 2003 - 2004
Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research(基盤研究(A)) 基盤研究(A)
Shigeo OHNO, 水野 恵子, 鈴木 厚, 平井 秀一, 秋本 和憲
Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid) Grant type：Competitive
Grant amount：\47320000 （ Direct Cost: \36400000 、 Indirect Cost：\10920000 ）
Eukaryotes possess a system termed 'nonsense-mediated mRNA decay' (NMD) or 'mRNA surveillance', by which aberrant mRNAs with premature termination codons (PTCs) are removed from cells, thereby protecting them from accumulation of nonfunctional or potentially harmful polypeptides. Thus, Nonsense-mediated mRNA decay (NMD) is a quality control mechanism of mRNA. Proteins required for NMD (UPF1,2,3, and SMG-1, SMG-5,6,7) have been identified initially from yeast and C. elegans genetics but recent experiments on mammlas are revealing the physiological meaning and the molecular mechanism of NMD i...
Grant number：15570163 2003 - 2004
Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research(基盤研究(C)) 基盤研究(C)
Atsushi SUZUKI
Authorship：Principal investigator Grant type：Competitive
Grant amount：\3700000 （ Direct Cost: \3700000 ）
aPKC and PAR-1 are required for cell polarity in various contexts. In mammalian epithelial cells, aPKC localizes at tight junctions (TJs) and plays an indispensable role in the development of asymmetric intracellular junctions essential for the establishment and the maintenance of apicobasal polarity. On the other hand, one of the mammalian PAR-1 kinases, PAR-1b/EMK1/MARK2, localizes to the lateral membrane in a complimentary manner with aPKC, but little is known about its role in apicobasal polarity of epithelial cells as well as its functional relationship with aPKC.We demonstrate that PA...
Grant number：13680790 2001 - 2002
Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research(基盤研究(C)) 基盤研究(C)
Atsushi SUZUKI
Authorship：Principal investigator Grant type：Competitive
Grant amount：\3600000 （ Direct Cost: \3600000 ）
In this project, I have tried to clarify how a TPA-responsible PKC, nPKCη, is involved in the junctional development during epithelial cell polarization, especially, in the light of the correlation with TPA-unresponsible PKCs, aPKCs which we had shown to play critical role in the process. Essentially, we utilized a dominant negative mutant of nPKCη (n OKCηkn) to specifically suppress the activity of nPKCη during a calcium switch-induced junctional formation or TPA-induced tight junction (TJ)-like structure formation.nPKCηkn-overexpressed MDCK cells failed to restore TJs as well as adherents...
Functional analysis of atypical OKC and ASIP in cardiovascular diseases
Grant number：13670733 2001 - 2002
Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research(基盤研究(C)) 基盤研究(C)
Satoshi UMEMURA, 鈴木 厚
Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid) Grant type：Competitive
Grant amount：\3700000 （ Direct Cost: \3700000 ）
Protein Kinase C (PKC) signaling pathway is involved in a variety of biological functions. Since activation of PKC pathway has been implicated in the development of cardiomyocyte hypertrophy, inhibition of this pathway would be an attractive target for the suppression of cardiomyocyte hypertrophy. Previous reports suggest that conventional PKC and novel PKC cause hypertrophic responses. We have recently focused our studies of PKC on atypical PKC, the third class of PKC family which is TPA and Ca2+insensitive and atypical PKC specific interacting protein (ASIP).EGF are known to induce hypert...
細胞極性決定因子aPKC/ASIPの哺乳類初期発生及び器官形成における役割の解析
Grant number：13045039 2001
文部科学省 科学研究費補助金(特定領域研究(A)) 特定領域研究(A)
秋本 和憲, 鈴木 厚
Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid) Grant type：Competitive
Grant amount：\2900000 （ Direct Cost: \2900000 ）
a)哺乳類初期発生におけるaPKC/ASIPの役割の解析 1)免疫組織学的な解析の結果、胎生7.5日ΔaPKCマウスの異常な胚性外胚葉を構成する上皮様細胞で一部の細胞接着分子マーカーの挙動が異常であった。更に、電子顕微鏡解析により、この異常な細胞で実際に細胞間接着構造が異常となっていることが確かめられた。2)この異常な胚性外胚葉を構成する上皮様細胞ではaPKC結合蛋白であり、かつ細胞極性マーカーであるASIPとPar6の細胞内局在が異常であった。3)この異常な上皮様細胞では細胞の分裂軸が異常であった。つまり、ΔaPKCマウスの異常な胚性外胚葉を構成する上皮様細胞においては細胞極性が異常となっていた。以上から、aPKCは哺乳類初期発生過程において、胚性外胚葉を構成する上皮細胞の細胞極性制御に必須であり、この極性制御を介して胚性外胚葉の組織構築に重要な役割を果たしていることが明らかとなった。このことは、不明な点の多い哺乳類初期胚の胚性外胚葉の発生メカニズムの一端に新たなメスを入れるものである。更に、線虫やショウジョウバエばかりではなく哺乳類の初期発生においても保存された多細胞生物共通のaPKCを介した細胞極性制御メカニズムの存在が本研究により明らかとなった。b)中枢神経形成 aPKC/ASIPは脳室帯の神経幹細胞において脳室に面した頂端側に極性を持って局在しており、aPKC/AS...
Signaling mechanism of epithelial cell-cell attachment and cell polarity.
Grant number：12219215 2000 - 2004
Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research(特定領域研究(C), 特定領域研究) 特定領域研究(C), 特定領域研究
Shigeo OHNO, 杉山 由樹, 秋本 和憲, 水野 恵子, 鈴木 厚
Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid) Grant type：Competitive
Grant amount：\269200000 （ Direct Cost: \269200000 ）
Epithelial cells represent the fundamental cell type in metazoa, which constitute sheets covering surface and make boundary between the interior and exterior of the organism. They not only work as selective permeability barriers, but also play active physiological roles such as adsorption and secretion. Furthermore, they provide driving forces of dynamic morphogenesis for development through the considerable plasticity in their structural organization. Recent progress in understanding evolutionarily-conserved cell polarity-machinery has provided significant insight in the mechanism by which...
Analyses of the universal molecular machinary involved in cell polarization
Grant number：11480182 1999 - 2000
Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research(基盤研究(B)) 基盤研究(B)
Shigeo OHNO, 秋本 和憲, 鈴木 厚, 平井 秀一
Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid) Grant type：Competitive
Grant amount：\15400000 （ Direct Cost: \15400000 ）
We as well as other people working on C.elegans and Drosophia revealed that aPKC, PAR-3 and PAR-6 are polarity proteins that co-operate in the establishment of cell polarity in C.elegans and Drosophila embryos. These three proteins co-localize asymjmetrically in C.elegans one-cell ambryo and in Drosophial epithelial cells and neuroblasts. Here we have shown that, in mammalian elitheial cells, these three proteins co-localize to the apical end of the junctional complex, tight junctions. Furthermore, we have shown that aPKC is required for the formation of the epithelia-specific cell-cell jun...
上皮細胞極性形成・維持におけるASIP-aPKCシステムの役割の研究
Grant number：11780518 1999 - 2000
文部科学省 科学研究費補助金(奨励研究(A)) 奨励研究(A)
鈴木 厚
Authorship：Principal investigator Grant type：Competitive
Grant amount：\2200000 （ Direct Cost: \2200000 ）
本年度の最大の成果は、「MDCK上皮培養細胞へのaPKCの優性抑制変異体の導入が、細胞接着によって誘導されるタイトジャンクション(TJ)形成、および上皮極性の発達を阻害する」という、一昨年発見し、昨年度に深化させた知見を論文にして発表することを目指し、裏面に示す通りこの目標を達成したことである。この中で、線虫PAR-6の哺乳動物ホモログもaPKC、ASIP/PAR-3とともに複合体を形成し、上皮細胞のTJに濃縮していることも明らかとし、上記aPKCの細胞極性形成における機能が、線虫と同様に進化的に保存されたPARタンパク質群と相互作用する中で発揮されている可能性をさらに強く示唆することができた。この論文は、哺乳動物細胞において、aPKCがPARシステムとともに上皮極性に必須な役割をしていることをはじめて示した論文であり、今後の研究の発展に結びつく大きな成果であると確信している。一方、本年は、aPKCのキナーゼ活性が接着構造形成のどの素過程に必須な役割を果たしているのかと明らかにするために、MDCK/カルシウムスイッチの系よりも上皮細胞接着構造・極性形成過程をゆっくりと追跡できるMTD1A細胞/創傷治癒モデル実験系を新たに導入し、これを利用してaPKC優性抑制変異体の効果をさらに詳細に解析した。その結果、aPKCはE-cadherin、ZO-1などが作る初期の点状のアドへレンス...
Grant number：11153221 1999
文部科学省 科学研究費補助金(特定領域研究(A)) 特定領域研究(A)
鈴木 厚
Authorship：Principal investigator Grant type：Competitive
Grant amount：\1800000 （ Direct Cost: \1800000 ）
本研究補助金を利用することによって、すでに我々が筋肉に特異性が高い新規の低分子量熱ショックタンパク質(sHSP)として同定・命名していたMKBPの構造機能相関に関する研究を大きく進展させることができた。この結果、今後MKBPの生理的機能をさらに検討していく上で有用となる、変異体を設計するための基礎データを得ることができた。哺乳動物の筋肉中に多量に発現しているsHSPは5種存在し、それらが非常に選択的な相互作用を示すことによって2つの独立した会合体を形成していることを、我々はすでに明らかとしている。その中で、MKBPはホモ会合活性を示すとともに、HSBP3とも結合する。まず、こうしたMKBPの選択的会合特性に関与する分子上の領域を酵母two-hybrid systemを利用して検討した。そして、1)当初の予想に反して、選択的なホモ会合、およびHSPB3との結合両方に、MKBPを特異的な配列が存在するN、またはC末端は必要ではなく、むしろsHSP全般に保存されたα-crystallinドメインが関与していること、2)しかし、その2種の結合に必須な領域は微妙に異なり、ホモ会合にはその前半部分、HSPB3との結合にはこのドメイン全体が必須であること、3)MKBPの生理的気質と考えられる、筋強直性ジストロフィーキナーゼ(DMPK)との結合もやはりこのα-crystallinドメインのよ...
Grant number：09770103 1997 - 1998
文部科学省 科学研究費補助金(奨励研究(A)) 奨励研究(A)
鈴木 厚
Authorship：Principal investigator Grant type：Competitive
Grant amount：\2200000 （ Direct Cost: \2200000 ）
今年度は、筋肉の維持に対する低分子量熱ショックタンパク質一般の重要性を検討することを主に進めた。具体的には、これまでに同定されてきている哺乳動物のsHSPファミリーメンバー6種のうち5種(レンズ特異的といわれるαA-crystallinを除く)に関して、そのcDNAおよび抗体を準備し、筋肉をキーワードとしてこれらすべてを対象とした基本的な定性(発現の組織分布、筋分化にともなう発現誘導の有無、相互作用、筋肉内での会合状態、熱ショックに対する初期応答、および後期応答、筋培養細胞中での局在)を系統的に進めた。特に、これまで塩基配列しか報告されていなかったHSPB3についてもそのクローニングと抗体作成を行い、初めて基本的な定性を進めた。その中で以下の諸結果が得られた(現在、論文を投稿中)。1)5種すべてのsHSPが、程度の差はあれ、筋肉に高い特異性をもって高濃度に発現している。特に、MKBP,HSPB3の発現は基本的に骨格筋、心筋にしかみられず、これらの組織における機能的重要性が示唆された。2)5種sHSPsがそのアミノ酸配列の相同性にも関わらず、互いに非常に選択性のある相互作用を示す。さらに心筋可溶性画分を生化学的に解析した結果、5種のsHSPが、主としてHSP27/aB-crystallin/p20、およびMKBP/HSPB3からなる2種の独立した、相互排除的な会合体として存在し...
Manipulation of the interaction between protein kinase C and its specific substrate proteins
Grant number：09558088 1997 - 1998
Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research(基盤研究(B)) 基盤研究(B)
Shigeo OHNO, 水野 恵子, 鈴木 厚
Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid) Grant type：Competitive
Grant amount：\12600000 （ Direct Cost: \12600000 ）
Protein kinase C (PKC) has been implicated in a variety of cellular responses that include cell growth, differentiation, and apoptosis, as well as responses to a variety of physiological signals and artificial stresses. Thus, it is very important to manipulate the function of PKC in a specific manner for pharmacological manipulation of the cellular signaling cascades as well as basic research for the understanding of the intracellular signaling network. In the present study, we searched for specific binding proteins for several isotypes of the PKC family and examined the physiological meani...
Two-hybrid systemを利用したPKC標的タンパク質の同定と解析
Grant number：08770108 1996
文部科学省 科学研究費補助金(奨励研究(A)) 奨励研究(A)
鈴木 厚
Authorship：Principal investigator Grant type：Competitive
Grant amount：\900000 （ Direct Cost: \900000 ）
昨年度クローニングに成功した新規PKCε結合タンパク質、εBP,の生理的役割を明らかにすべくさらに研究を進め、以下のような結果を得た。1.大腸菌で発現、精製したεBPタンパク質を用いたin vitroの実験から、εBP上のPKCεリン酸化部位がそのBTBドメインにはなく、それよりC末端側にあることが明らかとなった。2.COS細胞内に高発現したεBPおよびPKCεキナーゼドメインが核内粒子構造に共局在するという現象を利用して、BTBドメインに続くα-helical coiled coil構造をとることが強く示唆されている80アミノ酸を含む領域がPCKとの細胞内相互作用に重要であることを明らかとした。この結果は、1.で述べたin vitroリン酸化の結果と一致する。3.各種組織のDNAライブラリーに対してPCRを行いサザンブロットによる解析を行ったところ、クローニングの過程から予想されていた以上の組織依存的な多様な可変スプライシングとそれに由来するアイソフォームの存在が明らかとなった。4.最新の遺伝子データベースの解析から、εBPのBTBドメイン周辺の構造は細胞膜の裏打ち構造タンパクと考えられているkelchと最も相同性の高いことがさらに強く示唆された。またこの領域は雌配偶子の減数分裂異常変異体から同定された線虫のmel-26 gene産物とも相同性が高いこともわかった。BTBド...
Grant number：07278238 1995
文部科学省 科学研究費補助金(重点領域研究) 重点領域研究
鈴木 厚
Authorship：Principal investigator Grant type：Competitive
Grant amount：\2000000 （ Direct Cost: \2000000 ）
神経可塑性に関わる情報伝達機構の解明を目指して、キナーゼ結合タンパク質の検索をヒト脳cDNAライブラリーにおいて酵母Two-hybrid systemを利用して行った。可塑性への関与が指摘されているPKCεのキナーゼドメインをプローブとしたスクリーニングでは最終的に新規タンパク質εBP1のクローニングを完了し、その機能解析を進め、現在論文化を急いでいる。また、我々が新規に同定したMAPKKKホモログであり、JNK活性化に関わっていることが最近明らかとなったMUKをプローブとしたスクリーニングでは、現在9種以上ののポジティブクローンを同定するに至っており、最終的なクローニングを進行中である。前者のεBP1は、脳・筋肉を中心に普遍的に発現しており、近年新しいタンパク-タンパク相互作用interfaceとして注目されてきているBTB/POZドメインを含むタンパク質ファミリーの一員であることがわかった。このファミリーは、このドメインのホモ/ヘテロ多量体形成活性を介して細胞内で大きな構造体を形成し、クロマチン構造制御を通じた遺伝子発現制御、あるいは細胞骨格系の形成に関与していることが指摘さている。εBP1をCOS細胞に強制発現させた場合、アイソフォーム依存的にBTB/POZドメインタンパク質に特徴的といわれる核内粒子構造や細胞質の繊維状の会合体への局在を示し、また、Hela細胞などの内...
Two-hybrid systemを利用したPKC標的タンパク質の同定と解析
Grant number：07770110 1995
文部科学省 科学研究費補助金(奨励研究(A)) 奨励研究(A)
鈴木 厚
Authorship：Principal investigator Grant type：Competitive
Grant amount：\800000 （ Direct Cost: \800000 ）
初期の目的を基本的に達成し、酵母Two-hybrid systemにより、PKCεのキナーゼドメインに特異的に結合する新規ヒトタンパク質、εBP1を、クローニングすることに成功した。タンパク質発現が困難なため生化学的な解析が遅れているが、以下の興味深い知見がすでに得られており、早急に発表したいと考えている。1.εBP1は、新しいタンパク-タンパク相互作用interfaceとして近年注目されているBTB/POZドメインを含むタンパク質ファミリーの一員であった。このドメインは、ホモ/ヘテロ多量体形成活性を介して細胞内で大きな構造体を形成し、クロマチン構造制御を通じた遺伝子発現制御、あるいは細胞骨格系の形成に関与していることが指摘されている。ヒト白血病の2種の癌原遺伝子(Bcl6/LAZ3、およびPLZF)がこのファミリーに属することも報告されている。ノーザンブロットの結果からは、eBP1が脳、筋肉を中心として普遍的に発現していることが明からとなった。2.εBP1はそのN末端のBTB/POZドメイン周辺において非常に複雑な可変スプライシングを受け、多様なアイソフォームとして発現している。3.COS細胞に強制発現させると、εBP1はアイソフォーム依存的な、しかしBTB/POZドメインタンパク質に特徴的な細胞内局在、すなわち、核内粒子様構造への局在、あるいは細胞質での巨大な繊維状の会合...
Grant number：06283222 1994 - 1996
文部科学省 科学研究費補助金(重点領域研究) 重点領域研究
大野 茂男, 平井 秀一, 長田 真一, 水野 恵子, 鈴木 厚
Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid) Grant type：Competitive
Grant amount：\37000000 （ Direct Cost: \37000000 ）
PKCは細胞内シグナル経路の調節因子として極めて重要であることが様々な実験から推測されてきたが、未だにその具体的な作用点は不明である。本研究では、従来の研究で集積したPKCに関する独自の材料を用いて、PKCの具体的な作用点を解明することを目的とし、以下の二つの方向からのアプローチを行い、以下の結果を得た。1)PI3キナーゼ経路の代表的な下流因子、p70S6キナーゼの活性化機構を解析し、これにaPKCλが関わっていることを明らかにした。2)nPKCδ結合蛋白質として細胞膜貫通型のタンパク質を同定した。これはメタロプロテイナーゼ/ディスインテグリンファミリーの仲間であり、PKCδはこの細胞質ドメインに特異的に結合する。細胞接着とシグナル伝達経路との接点となっている事が予測され、きわめて興味深い。3)aPKCλ結合タンパク質として、PDZドメインを有する新規タンパク質を見いだした。これは線虫の卵の不等分裂に関わる遺伝子のほ乳類版であった。4)Rafを介したMAPキナーゼの活性化過程において、Ras以外に必要な因子として、PKCδを同定した。5)ストレス応答MAPキナーゼ(SAPK/JNK)経路の上流キナーゼとして、MUK、MST/MLK2を同定し、これらがSEKを介してSAPK/JNKを活性化することを示した。SAPK/JNKの上流には、MEKKに加えてMUK/MLKファミリーが存...
Study on molecular mechanism of cell polarity biogenesis in mammalian epitherial cells
Grant type：Competitive
初期細胞基質接着に必須な役割を果たす、ILK-affixinシグナル伝達系の解析
Grant type：Competitive
Study on a ILK-affixin signaling which is essential for the initial formation of focal adhesion
Grant type：Competitive
哺乳動物上皮細胞の細胞極性形成機構の研究
Grant type：Competitive
