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ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration

The cellular events that precede myelination in the peripheral nervous system require rapid and dynamic morphological changes in the Schwann cell. These events are thought to be mainly controlled by axonal signals. But how signals on the axons are coordinately organized and transduced to promote pro...

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Detalles Bibliográficos
Autores principales: Yamauchi, Junji, Miyamoto, Yuki, Chan, Jonah R., Tanoue, Akito
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2315680/
https://www.ncbi.nlm.nih.gov/pubmed/18426980
http://dx.doi.org/10.1083/jcb.200709033
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author Yamauchi, Junji
Miyamoto, Yuki
Chan, Jonah R.
Tanoue, Akito
author_facet Yamauchi, Junji
Miyamoto, Yuki
Chan, Jonah R.
Tanoue, Akito
author_sort Yamauchi, Junji
collection PubMed
description The cellular events that precede myelination in the peripheral nervous system require rapid and dynamic morphological changes in the Schwann cell. These events are thought to be mainly controlled by axonal signals. But how signals on the axons are coordinately organized and transduced to promote proliferation, migration, radial sorting, and myelination is unknown. We describe that the axonal signal neuregulin-1 (NRG1) controls Schwann cell migration via activation of the atypical Dock180-related guanine nucleotide exchange factor (GEF) Dock7 and subsequent activation of the Rho guanine triphosphatases (GTPases) Rac1 and Cdc42 and the downstream c-Jun N-terminal kinase. We show that the NRG1 receptor ErbB2 directly binds and activates Dock7 by phosphorylating Tyr-1118. Dock7 knockdown, or expression of Dock7 harboring the Tyr-1118–to–Phe mutation in Schwann cells, attenuates the effects of NRG1. Thus, Dock7 functions as an intracellular substrate for ErbB2 to promote Schwann cell migration. This provides an unanticipated mechanism through which ligand-dependent tyrosine phosphorylation can trigger the activation of Rho GTPase-GEFs of the Dock180 family.
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spelling pubmed-23156802008-10-21 ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration Yamauchi, Junji Miyamoto, Yuki Chan, Jonah R. Tanoue, Akito J Cell Biol Research Articles The cellular events that precede myelination in the peripheral nervous system require rapid and dynamic morphological changes in the Schwann cell. These events are thought to be mainly controlled by axonal signals. But how signals on the axons are coordinately organized and transduced to promote proliferation, migration, radial sorting, and myelination is unknown. We describe that the axonal signal neuregulin-1 (NRG1) controls Schwann cell migration via activation of the atypical Dock180-related guanine nucleotide exchange factor (GEF) Dock7 and subsequent activation of the Rho guanine triphosphatases (GTPases) Rac1 and Cdc42 and the downstream c-Jun N-terminal kinase. We show that the NRG1 receptor ErbB2 directly binds and activates Dock7 by phosphorylating Tyr-1118. Dock7 knockdown, or expression of Dock7 harboring the Tyr-1118–to–Phe mutation in Schwann cells, attenuates the effects of NRG1. Thus, Dock7 functions as an intracellular substrate for ErbB2 to promote Schwann cell migration. This provides an unanticipated mechanism through which ligand-dependent tyrosine phosphorylation can trigger the activation of Rho GTPase-GEFs of the Dock180 family. The Rockefeller University Press 2008-04-21 /pmc/articles/PMC2315680/ /pubmed/18426980 http://dx.doi.org/10.1083/jcb.200709033 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Yamauchi, Junji
Miyamoto, Yuki
Chan, Jonah R.
Tanoue, Akito
ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration
title ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration
title_full ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration
title_fullStr ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration
title_full_unstemmed ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration
title_short ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration
title_sort erbb2 directly activates the exchange factor dock7 to promote schwann cell migration
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2315680/
https://www.ncbi.nlm.nih.gov/pubmed/18426980
http://dx.doi.org/10.1083/jcb.200709033
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