記述言語：英語   出版者・発行元：WILEY-BLACKWELL  

During developing nervous system, neurons project axons to their targets precisely. In this process, axon guidance molecules provide positional information to the axons. Therefore, the spatially and temporally controlled localization of the axon guidance molecules is required for the proper structure formation of the complex nervous system. In C.elegans, UNC-6/Netrin is a secreted protein that elicits both attractive and repulsive response in axon guidance. UNC-6/Netrin secreted from ventral cells may establish a concentration gradient from the ventral to the dorsal side of the animal, thus providing dorso-ventral positional information. However, the mechanisms specifying positional information of UNC-6/Netrin are largely unknown. Here, we show that the ire-1/xbp-1 pathway of the unfolded protein response (UPR) is required for axonal distribution of UNC-6/Netrin in the ventral neurons. In addition, the ire-1/xbp-1 pathway is also required for dorso-ventral axon guidance mediated by UNC-6/Netrin. Our results suggest that the ire-1/xbp-1 pathway of the UPR is crucial for establishing positional information of UNC-6/Netrin. We propose that the proper secretion of UNC-6/Netrin from the ventral neurons requires the activity of IRE-1.

DOI： 10.1111/gtc.12206

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記述言語：英語   出版者・発行元：NATURE PUBLISHING GROUP  

Reorganization of the actin cytoskeleton is an early cellular response to various extracellular signals. Sema3A, a repulsive axon guidance molecule, induces the reorganization of actin cytoskeleton in the growth cones. Collapsin response mediator protein 1 (CRMP1) mediates the intracellular Sema3A signalling through its Ser522 phosphorylation. Here we show that UNC-33, CRMP1 C. elegans homologue, interacts with FLN-1, an actin-binding Filamin-A orthologue. In nematodes, this interaction participates in the projection of DD/VD motor neurons. CRMP1 binds both the actin-binding domain and the last immunoglobulin-like repeat of Filamin-A. The alanine mutants of Filamin-A or CRMP1 in their interacting residues suppress the Sema3A repulsion in neurons. Conversely, a phosphor-mimicking mutant CRMP1(Ser522Asp) enhances the Sema3A response. Atomic-force microscopy analysis reveals that the V-shaped Filamin-A changes to a condensed form with CRMP1(Ser522Asp). CRMP1(Ser522Asp) weakens the F-actin gelation crosslinked by Filamin-A. Thus, phosphorylated CRMP1 may remove Filamin-A from the actin cytoskeleton to facilitate its remodelling.

DOI： 10.1038/ncomms6325

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記述言語：英語   掲載種別：書評論文，書評，文献紹介等   出版者・発行元：WILEY-BLACKWELL  

Netrin is an evolutionarily conserved, secretory axon guidance molecule. Netrin's receptors, UNC-5 and UNC-40/DCC, are single trans-membrane proteins with immunoglobulin domains at their extra-cellular regions. Netrin is thought to provide its positional information by establishing a concentration gradient. UNC-5 and UNC-40 act at growth cones, which are specialized axonal tip structures that are generally located at a long distance from the neural cell body. Thus, the proper localization of both Netrin and its receptors is critical for their function. This review addresses the localization mechanisms of UNC-6/Netrin and its receptors in Caenorhabditis similar to elegans, focusing on our recent reports. These findings include novel insights on cytoplasmic proteins that function upstream of the receptors.

DOI： 10.1111/j.1440-169X.2012.01349.x

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記述言語：英語   出版者・発行元：SOC NEUROSCIENCE  

The ability to detect harmful chemicals rapidly is essential for the survival of all animals. In Caenorhabditis elegans (C. elegans), repellents trigger an avoidance response, causing animals to move away from repellents. Dihydrocaffeic acid (DHCA) is a water-soluble repellent and nonflavonoid catecholic compound that can be found in plant products. Using a Xenopus laevis (X. laevis) oocyte expression system, we identified a candidate dihydrocaffeic acid receptor (DCAR), DCAR-1. DCAR-1 is a novel seven-transmembrane protein that is expressed in the ASH avoidance sensory neurons of C. elegans. dcar-1 mutant animals are defective in avoidance response to DHCA, and cell-specific expression of dcar-1 in the ASH neurons of dcar-1 mutant animals rescued the defect in avoidance response to DHCA. Our findings identify DCAR-1 as the first seven-transmembrane receptor required for avoidance of a water-soluble repellent, DHCA, in C. elegans.

DOI： 10.1523/JNEUROSCI.4018-11.2011

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記述言語：英語   出版者・発行元：WILEY-BLACKWELL  

Oxygen is essential for animals, but high concentrations of oxygen are toxic to them probably because of an increase in reactive oxygen species (ROS). Many genes are involved in the reactions from which ROS are generated, but not much attention has been focused on them. To identify these genes, we screened for mutants with an altered sensitivity to oxidative stress in the nematode Caenorhabditis elegans and isolated a mutant, oxy-5(qa5002). oxy-5 showed an increased sensitivity to oxygen and decreased longevity. The decreased life span in oxy-5 was probably due to increased oxidative stress because it was recovered to a normal level when oxy-5 was cultured under hypoxic conditions. Our genetic analysis has revealed that the responsible gene for oxy-5 encodes a protein similar to mitochondrial ribosomal protein S36. The OXY-5 protein was highly expressed in the neurons, pharynx, and intestine, and expression of oxy-5 from the pan-neuronal H20 promoter efficiently suppressed the increased sensitivity to oxygen in oxy-5. These findings suggested that oxy-5 played an important role in the regulation of the sensitivity to oxygen in neuronal cells in C. elegans.

DOI： 10.1111/j.1365-2443.2010.01469.x

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