title: The C. elegans Discoidin Domain Receptor DDR-2 Modulates the Met-like RTK-JNK Signaling Pathway in Axon Regeneration.
abstract: The ability of specific neurons to regenerate their axons after injury is governed by cell-intrinsic regeneration pathways. However, the signaling pathways that orchestrate axon regeneration are not well understood. In Caenorhabditis elegans, initiation of axon regeneration is positively regulated by SVH-2 Met-like growth factor receptor tyrosine kinase (RTK) signaling through the JNK MAPK pathway. Here we show that SVH-4/DDR-2, an RTK containing a discoidin domain that is activated by collagen, and EMB-9 collagen type IV regulate the regeneration of neurons following axon injury. The scaffold protein SHC-1 interacts with both DDR-2 and SVH-2. Furthermore, we demonstrate that overexpression of svh-2 and shc-1 suppresses the delay in axon regeneration observed in ddr-2 mutants, suggesting that DDR-2 functions upstream of SVH-2 and SHC-1. These results suggest that DDR-2 modulates the SVH-2-JNK pathway via SHC-1. We thus identify two different RTK signaling networks that play coordinated roles in the regulation of axonal regeneration.
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hisamoto
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, Japan.
authors.forename: Yuki
authors.identifier: http://orcid.org/0000-0002-0013-4047
authors.initials: Y
authors.lastname: Nagamori
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, Japan.
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, Japan.
authors.forename: Strahil I
authors.identifier: http://orcid.org/0000-0002-5871-7149
authors.initials: SI
authors.lastname: Pastuhov
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D001369:Axons / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D000070822:Discoidin Domain / Q000235:genetics; D000070820:Discoidin Domain Receptor 2 / Q000235:genetics* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009416:Nerve Regeneration / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; C000618260:SHC-1 protein, C elegans; D000070820:Discoidin Domain Receptor 2; D020794:Receptor Protein-Tyrosine Kinases; C000618261:SVH-2 protein, C elegans; D048031:JNK Mitogen-Activated Protein Kinases