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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...

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Autores principales: Hisamoto, Naoki, Nagamori, Yuki, Shimizu, Tatsuhiro, Pastuhov, Strahil I., Matsumoto, Kunihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
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.
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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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