p130CASIs 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 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.