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 (2012). Growth cone MKK7 mRNA targeting regulates MAP1b-dependent microtubule bundling to control neurite elongation. PLoS biology, 10(12), e1001439. Public Library of Science 10.1371/journal.pbio.1001439

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Pertz, Olivier

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

1544-9173

Publisher:

Public Library of Science

Language:

English

Submitter:

Olivier Pertz

Date Deposited:

03 May 2016 10:24

Last Modified:

06 May 2016 05:25

Publisher DOI:

10.1371/journal.pbio.1001439

PubMed ID:

23226105

BORIS DOI:

10.7892/boris.81858

URI:

https://boris.unibe.ch/id/eprint/81858

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