Growth Cone MKK7 mRNA Targeting Regulates MAP1b-Dependent Microtubule Bundling to Control Neurite Elongation

被引：37

作者：

Feltrin, Daniel ^{[1
]}

Fusco, Ludovico ^{[1
]}

Witte, Harald ^{[2
]}

Moretti, Francesca ^{[1
]}

Martin, Katrin ^{[1
]}

Letzelter, Michel ^{[1
]}

Fluri, Erika ^{[1
]}

Scheiffele, Peter ^{[2
]}

Pertz, Olivier ^{[1
]}

机构：

[1] Univ Basel, Dept Biomed, Inst Biochem & Genet, Basel, Switzerland

[2] Univ Basel, Biozentrum, Basel, Switzerland

来源：

PLOS BIOLOGY | 2012年 / 10卷 / 12期

基金：

瑞士国家科学基金会;

关键词：

N-TERMINAL KINASE; DEVELOPING CEREBRAL-CORTEX; LOCAL PROTEIN-SYNTHESIS; HIPPOCAMPAL-NEURONS; PERIPHERAL-NERVE; AXON FORMATION; ACTIN; REVEALS; PHOSPHORYLATION; LOCALIZATION;

D O I：

10.1371/journal.pbio.1001439

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：23