Cargando…
Growth Cone MKK7 mRNA Targeting Regulates MAP1b-Dependent Microtubule Bundling to Control Neurite Elongation
Local mRNA translation in neurons has been mostly studied during axon guidance and synapse formation but not during initial neurite outgrowth. We performed a genome-wide screen for neurite-enriched mRNAs and identified an mRNA that encodes mitogen-activated protein kinase kinase 7 (MKK7), a MAP kina...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514283/ https://www.ncbi.nlm.nih.gov/pubmed/23226105 http://dx.doi.org/10.1371/journal.pbio.1001439 |
_version_ | 1782252007013220352 |
---|---|
author | Feltrin, Daniel Fusco, Ludovico Witte, Harald Moretti, Francesca Martin, Katrin Letzelter, Michel Fluri, Erika Scheiffele, Peter Pertz, Olivier |
author_facet | Feltrin, Daniel Fusco, Ludovico Witte, Harald Moretti, Francesca Martin, Katrin Letzelter, Michel Fluri, Erika Scheiffele, Peter Pertz, Olivier |
author_sort | Feltrin, Daniel |
collection | PubMed |
description | Local mRNA translation in neurons has been mostly studied during axon guidance and synapse formation but not during initial neurite outgrowth. We performed a genome-wide screen for neurite-enriched mRNAs and identified an mRNA that encodes mitogen-activated protein kinase kinase 7 (MKK7), a MAP kinase kinase (MAPKK) for Jun kinase (JNK). We show that MKK7 mRNA localizes to the growth cone where it has the potential to be translated. MKK7 is then specifically phosphorylated in the neurite shaft, where it is part of a MAP kinase signaling module consisting of dual leucine zipper kinase (DLK), MKK7, and JNK1. This triggers Map1b phosphorylation to regulate microtubule bundling leading to neurite elongation. We propose a model in which MKK7 mRNA localization and translation in the growth cone allows for a mechanism to position JNK signaling in the neurite shaft and to specifically link it to regulation of microtubule bundling. At the same time, this uncouples activated JNK from its functions relevant to nuclear translocation and transcriptional activation. |
format | Online Article Text |
id | pubmed-3514283 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35142832012-12-05 Growth Cone MKK7 mRNA Targeting Regulates MAP1b-Dependent Microtubule Bundling to Control Neurite Elongation Feltrin, Daniel Fusco, Ludovico Witte, Harald Moretti, Francesca Martin, Katrin Letzelter, Michel Fluri, Erika Scheiffele, Peter Pertz, Olivier PLoS Biol Research Article Local mRNA translation in neurons has been mostly studied during axon guidance and synapse formation but not during initial neurite outgrowth. We performed a genome-wide screen for neurite-enriched mRNAs and identified an mRNA that encodes mitogen-activated protein kinase kinase 7 (MKK7), a MAP kinase kinase (MAPKK) for Jun kinase (JNK). We show that MKK7 mRNA localizes to the growth cone where it has the potential to be translated. MKK7 is then specifically phosphorylated in the neurite shaft, where it is part of a MAP kinase signaling module consisting of dual leucine zipper kinase (DLK), MKK7, and JNK1. This triggers Map1b phosphorylation to regulate microtubule bundling leading to neurite elongation. We propose a model in which MKK7 mRNA localization and translation in the growth cone allows for a mechanism to position JNK signaling in the neurite shaft and to specifically link it to regulation of microtubule bundling. At the same time, this uncouples activated JNK from its functions relevant to nuclear translocation and transcriptional activation. Public Library of Science 2012-12-04 /pmc/articles/PMC3514283/ /pubmed/23226105 http://dx.doi.org/10.1371/journal.pbio.1001439 Text en © 2012 Feltrin 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Feltrin, Daniel Fusco, Ludovico Witte, Harald Moretti, Francesca Martin, Katrin Letzelter, Michel Fluri, Erika Scheiffele, Peter Pertz, Olivier Growth Cone MKK7 mRNA Targeting Regulates MAP1b-Dependent Microtubule Bundling to Control Neurite Elongation |
title | Growth Cone MKK7 mRNA Targeting Regulates MAP1b-Dependent Microtubule Bundling to Control Neurite Elongation |
title_full | Growth Cone MKK7 mRNA Targeting Regulates MAP1b-Dependent Microtubule Bundling to Control Neurite Elongation |
title_fullStr | Growth Cone MKK7 mRNA Targeting Regulates MAP1b-Dependent Microtubule Bundling to Control Neurite Elongation |
title_full_unstemmed | Growth Cone MKK7 mRNA Targeting Regulates MAP1b-Dependent Microtubule Bundling to Control Neurite Elongation |
title_short | Growth Cone MKK7 mRNA Targeting Regulates MAP1b-Dependent Microtubule Bundling to Control Neurite Elongation |
title_sort | growth cone mkk7 mrna targeting regulates map1b-dependent microtubule bundling to control neurite elongation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514283/ https://www.ncbi.nlm.nih.gov/pubmed/23226105 http://dx.doi.org/10.1371/journal.pbio.1001439 |
work_keys_str_mv | AT feltrindaniel growthconemkk7mrnatargetingregulatesmap1bdependentmicrotubulebundlingtocontrolneuriteelongation AT fuscoludovico growthconemkk7mrnatargetingregulatesmap1bdependentmicrotubulebundlingtocontrolneuriteelongation AT witteharald growthconemkk7mrnatargetingregulatesmap1bdependentmicrotubulebundlingtocontrolneuriteelongation AT morettifrancesca growthconemkk7mrnatargetingregulatesmap1bdependentmicrotubulebundlingtocontrolneuriteelongation AT martinkatrin growthconemkk7mrnatargetingregulatesmap1bdependentmicrotubulebundlingtocontrolneuriteelongation AT letzeltermichel growthconemkk7mrnatargetingregulatesmap1bdependentmicrotubulebundlingtocontrolneuriteelongation AT flurierika growthconemkk7mrnatargetingregulatesmap1bdependentmicrotubulebundlingtocontrolneuriteelongation AT scheiffelepeter growthconemkk7mrnatargetingregulatesmap1bdependentmicrotubulebundlingtocontrolneuriteelongation AT pertzolivier growthconemkk7mrnatargetingregulatesmap1bdependentmicrotubulebundlingtocontrolneuriteelongation |