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Coupled local translation and degradation regulate growth cone collapse

Local translation mediates axonal responses to Semaphorin3A (Sema3A) and other guidance cues. However, only a subset of the axonal proteome is locally synthesized, while most proteins are trafficked from the soma. The reason why only specific proteins are locally synthesized is unknown. Here we show...

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Detalles Bibliográficos
Autores principales: Deglincerti, Alessia, Colak, Dilek, Hengst, Ulrich, Liu, Yaobin, Xu, Guoqiang, Jaffrey, Samie R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408908/
https://www.ncbi.nlm.nih.gov/pubmed/25901863
http://dx.doi.org/10.1038/ncomms7888
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author Deglincerti, Alessia
Colak, Dilek
Hengst, Ulrich
Liu, Yaobin
Xu, Guoqiang
Jaffrey, Samie R.
author_facet Deglincerti, Alessia
Colak, Dilek
Hengst, Ulrich
Liu, Yaobin
Xu, Guoqiang
Jaffrey, Samie R.
author_sort Deglincerti, Alessia
collection PubMed
description Local translation mediates axonal responses to Semaphorin3A (Sema3A) and other guidance cues. However, only a subset of the axonal proteome is locally synthesized, while most proteins are trafficked from the soma. The reason why only specific proteins are locally synthesized is unknown. Here we show that local protein synthesis and degradation are linked events in growth cones. We find that growth cones exhibit high levels of ubiquitination and that local signaling pathways trigger the ubiquitination and degradation of RhoA, a mediator of Sema3A-induced growth cone collapse. Inhibition of RhoA degradation is sufficient to remove the protein-synthesis requirement for Sema3A-induced growth cone collapse. In addition to RhoA, we find that locally translated proteins are the main targets of the ubiquitin-proteasome system in growth cones. Thus, local protein degradation is a major feature of growth cones and creates a requirement for local translation to replenish proteins needed to maintain growth cone responses.
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spelling pubmed-44089082015-10-22 Coupled local translation and degradation regulate growth cone collapse Deglincerti, Alessia Colak, Dilek Hengst, Ulrich Liu, Yaobin Xu, Guoqiang Jaffrey, Samie R. Nat Commun Article Local translation mediates axonal responses to Semaphorin3A (Sema3A) and other guidance cues. However, only a subset of the axonal proteome is locally synthesized, while most proteins are trafficked from the soma. The reason why only specific proteins are locally synthesized is unknown. Here we show that local protein synthesis and degradation are linked events in growth cones. We find that growth cones exhibit high levels of ubiquitination and that local signaling pathways trigger the ubiquitination and degradation of RhoA, a mediator of Sema3A-induced growth cone collapse. Inhibition of RhoA degradation is sufficient to remove the protein-synthesis requirement for Sema3A-induced growth cone collapse. In addition to RhoA, we find that locally translated proteins are the main targets of the ubiquitin-proteasome system in growth cones. Thus, local protein degradation is a major feature of growth cones and creates a requirement for local translation to replenish proteins needed to maintain growth cone responses. 2015-04-22 /pmc/articles/PMC4408908/ /pubmed/25901863 http://dx.doi.org/10.1038/ncomms7888 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Deglincerti, Alessia
Colak, Dilek
Hengst, Ulrich
Liu, Yaobin
Xu, Guoqiang
Jaffrey, Samie R.
Coupled local translation and degradation regulate growth cone collapse
title Coupled local translation and degradation regulate growth cone collapse
title_full Coupled local translation and degradation regulate growth cone collapse
title_fullStr Coupled local translation and degradation regulate growth cone collapse
title_full_unstemmed Coupled local translation and degradation regulate growth cone collapse
title_short Coupled local translation and degradation regulate growth cone collapse
title_sort coupled local translation and degradation regulate growth cone collapse
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408908/
https://www.ncbi.nlm.nih.gov/pubmed/25901863
http://dx.doi.org/10.1038/ncomms7888
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