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Publication : Growth cone MKK7 mRNA targeting regulates MAP1b-dependent microtubule bundling to control neurite elongation.

First Author  Feltrin D Year  2012
Journal  PLoS Biol Volume  10
Issue  12 Pages  e1001439
PubMed ID  23226105 Mgi Jnum  J:194301
Mgi Id  MGI:5471918 Doi  10.1371/journal.pbio.1001439
Citation  Feltrin D, et al. (2012) Growth cone MKK7 mRNA targeting regulates MAP1b-dependent microtubule bundling to control neurite elongation. PLoS Biol 10(12):e1001439
abstractText  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.
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