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Nat Neurosci. 2004 Nov;7(11):1222-32. Epub 2004 Oct 17.

Netrin requires focal adhesion kinase and Src family kinases for axon outgrowth and attraction.

Author information

1
Department of Anatomy, Washington University School of Medicine, 660 South Euclid Ave., St. Louis, Missouri 63110, USA.

Abstract

Although netrins are an important family of neuronal guidance proteins, intracellular mechanisms that mediate netrin function are not well understood. Here we show that netrin-1 induces tyrosine phosphorylation of proteins including focal adhesion kinase (FAK) and the Src family kinase Fyn. Blockers of Src family kinases inhibited FAK phosphorylation and axon outgrowth and attraction by netrin. Dominant-negative FAK and Fyn mutants inhibited the attractive turning response to netrin. Axon outgrowth and attraction induced by netrin-1 were significantly reduced in neurons lacking the FAK gene. Our results show the biochemical and functional links between netrin, a prototypical neuronal guidance cue, and FAK, a central player in intracellular signaling that is crucial for cell migration.

PMID:
15494732
PMCID:
PMC2266630
DOI:
10.1038/nn1331
[Indexed for MEDLINE]
Free PMC Article

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