Reference - Detail
| RRC ID | 53381 |
|---|---|
| Author | Hisamoto N, Nagamori Y, Shimizu T, Pastuhov SI, Matsumoto K. |
| Title | The C. elegans Discoidin Domain Receptor DDR-2 Modulates the Met-like RTK-JNK Signaling Pathway in Axon Regeneration. |
| Journal | PLoS Genet |
| 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. |
| Volume | 12(12) |
| Pages | e1006475 |
| Published | 2016-12-1 |
| DOI | 10.1371/journal.pgen.1006475 |
| PII | PGENETICS-D-16-01050 |
| PMID | 27984580 |
| PMC | PMC5161311 |
| MeSH | Adaptor Proteins, Signal Transducing / genetics* Animals Axons / metabolism Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Discoidin Domain / genetics Discoidin Domain Receptor 2 / genetics* Discoidin Domain Receptor 2 / metabolism JNK Mitogen-Activated Protein Kinases / genetics JNK Mitogen-Activated Protein Kinases / metabolism Nerve Regeneration / genetics* Neurons / metabolism* Receptor Protein-Tyrosine Kinases / genetics* Receptor Protein-Tyrosine Kinases / metabolism Signal Transduction |
| IF | 5.175 |
| Times Cited | 5 |
| Resource | |
| C.elegans | tm797 tm737 |