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

Guofa Liu, Hilary Beggs, Claudia Jürgensen, Hwan Tae Park, Hao Tang, Jessica Gorski, Kevin R. Jones, Louis F. Reichardt, Jane Wu, Yi Rao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

210 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1222-1232
Number of pages11
JournalNature Neuroscience
Volume7
Issue number11
DOIs
StatePublished - Nov 1 2004

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Netrin requires focal adhesion kinase and Src family kinases for axon outgrowth and attraction'. Together they form a unique fingerprint.

Cite this