title: IRE-1/XBP-1 pathway of the unfolded protein response is required for properly localizing neuronal UNC-6/Netrin for axon guidance in C. elegans.
abstract: 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.
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Asakura
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ogura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000075385:Netrins; D009474:Neurons / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D056811:Unfolded Protein Response
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D000075385:Netrins; C078146:UNC-6 protein, C elegans; C548541:XBP-1 protein, C elegans; D017346:Protein Serine-Threonine Kinases; C541905:IRE-1 protein, C elegans