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Nat Cell Biol. 2009 Aug;11(8):1024-30. doi: 10.1038/ncb1916. Epub 2009 Jul 20.

Axonal elongation triggered by stimulus-induced local translation of a polarity complex protein.

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1
Department of Pharmacology, Weill Medical College, Cornell University, NY 10065, USA.

Abstract

During development, axon growth rates are precisely regulated to provide temporal control over pathfinding. The precise temporal regulation of axonal growth is a key step in the formation of functional synapses and the proper patterning of the nervous system. The rate of axonal elongation is increased by factors such as netrin-1 and nerve growth factor (NGF), which stimulate axon outgrowth using incompletely defined pathways. To clarify the mechanism of netrin-1- and NGF-stimulated axon growth, we explored the role of local protein translation. We found that intra-axonal protein translation is required for stimulated, but not basal, axon outgrowth. To identify the mechanism of translation-dependent outgrowth, we examined the PAR complex, a cytoskeleton regulator. We found that the PAR complex, like local translation, is required for stimulated, but not basal, outgrowth. Par3 mRNA is localized to developing axons, and NGF and netrin-1 trigger its local translation. Selective ablation of Par3 mRNA from axons abolishes the outgrowth-promoting effect of NGF. These results identify a new role for local translation and the PAR complex in axonal outgrowth.

PMID:
19620967
PMCID:
PMC2724225
DOI:
10.1038/ncb1916
[Indexed for MEDLINE]
Free PMC Article
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