p130CAS is required for netrin signaling and commissural axon guidance.

Liu G, Li W, Gao X, Li X, J├╝rgensen C, Park HT, Shin NY, Yu J, He ML, Hanks SK, Wu JY, Guan KL, Rao Y
J Neurosci. 2007 27 (4): 957-68

PMID: 17251438 · PMCID: PMC2014516 · DOI:10.1523/JNEUROSCI.4616-06.2007

Netrins are an important family of axon guidance cues. Here, we report that netrin-1 induces tyrosine phosphorylation of p130(CAS) (Crk-associated substrate). Our biochemical studies indicate that p130(CAS) is downstream of the Src family kinases and upstream of the small GTPase Rac1 and Cdc42. Inhibition of p130(CAS) signaling blocks both the neurite outgrowth-promoting activity and the axon attraction activity of netrin-1. p130(CAS) RNA interference inhibits the attraction of commissural axons in the spinal cord by netrin-1 and causes defects in commissural axon projection in the embryo. These results demonstrate that p130(CAS) is a key component in the netrin signal transduction pathway and plays an important role in guiding commissural axons in vivo.

MeSH Terms (15)

Animals Axons Cell Line Cells, Cultured Chick Embryo Crk-Associated Substrate Protein Female Humans MAP Kinase Signaling System Mice Nerve Growth Factors Netrin-1 Pregnancy rac1 GTP-Binding Protein Tumor Suppressor Proteins

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