p130CAS is required for netrin signaling and commissural axon guidance

Abstract

Netrins are an important family of axon guidance cues. Here, we report that netrin-1 induces tyrosine phosphorylation of p130CAS (Crk-associated substrate). Our biochemical studies indicate that p130CAS is downstream of the Src family kinases and upstream of the small GTPase Rac1 and Cdc42. Inhibition of p130CAS signaling blocks both the neurite outgrowth-promoting activity and the axon attraction activity of netrin-1. p130CAS 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 p130CAS is a key component in the netrin signal transduction pathway and plays an important role in guiding commissural axons in vivo. Copyright © 2007 Society for Neuroscience.