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The C. elegans Discoidin Domain Receptor DDR-2 Modulates the Met-like RTK–JNK Signaling Pathway in Axon Regeneration
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 b...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161311/ https://www.ncbi.nlm.nih.gov/pubmed/27984580 http://dx.doi.org/10.1371/journal.pgen.1006475 |
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author | Hisamoto, Naoki Nagamori, Yuki Shimizu, Tatsuhiro Pastuhov, Strahil I. Matsumoto, Kunihiro |
author_facet | Hisamoto, Naoki Nagamori, Yuki Shimizu, Tatsuhiro Pastuhov, Strahil I. Matsumoto, Kunihiro |
author_sort | Hisamoto, Naoki |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5161311 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-51613112017-01-04 The C. elegans Discoidin Domain Receptor DDR-2 Modulates the Met-like RTK–JNK Signaling Pathway in Axon Regeneration Hisamoto, Naoki Nagamori, Yuki Shimizu, Tatsuhiro Pastuhov, Strahil I. Matsumoto, Kunihiro PLoS Genet Research Article 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. Public Library of Science 2016-12-16 /pmc/articles/PMC5161311/ /pubmed/27984580 http://dx.doi.org/10.1371/journal.pgen.1006475 Text en © 2016 Hisamoto et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Hisamoto, Naoki Nagamori, Yuki Shimizu, Tatsuhiro Pastuhov, Strahil I. Matsumoto, Kunihiro The C. elegans Discoidin Domain Receptor DDR-2 Modulates the Met-like RTK–JNK Signaling Pathway in Axon Regeneration |
title | The C. elegans Discoidin Domain Receptor DDR-2 Modulates the Met-like RTK–JNK Signaling Pathway in Axon Regeneration |
title_full | The C. elegans Discoidin Domain Receptor DDR-2 Modulates the Met-like RTK–JNK Signaling Pathway in Axon Regeneration |
title_fullStr | The C. elegans Discoidin Domain Receptor DDR-2 Modulates the Met-like RTK–JNK Signaling Pathway in Axon Regeneration |
title_full_unstemmed | The C. elegans Discoidin Domain Receptor DDR-2 Modulates the Met-like RTK–JNK Signaling Pathway in Axon Regeneration |
title_short | The C. elegans Discoidin Domain Receptor DDR-2 Modulates the Met-like RTK–JNK Signaling Pathway in Axon Regeneration |
title_sort | c. elegans discoidin domain receptor ddr-2 modulates the met-like rtk–jnk signaling pathway in axon regeneration |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161311/ https://www.ncbi.nlm.nih.gov/pubmed/27984580 http://dx.doi.org/10.1371/journal.pgen.1006475 |
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