p130(CAS) is required for netrin signaling and commissural axon guidance

Liu G, Li W, Gao X, Li X, Jurgensen C, Park HT, Shin NY, Yu J, He ML, Hanks SK, Wu JY, Guan KL, Rao Y
Source: J Neurosci
Publication Date: (2007)
Issue: 27(4): 957-68
Research Area:
Cells used in publication:
Neuron, cortical, mouse
Species: mouse
Tissue Origin: brain
Nucleofectorâ„¢ I/II/2b
4x10e6 Cortical neurons isolated from E15 mouse embryos were co-nucleofected with 1 microgram Venus yellow fluorescent protein plus 4 micrograms control vector or 4 micrograms p130CAS shRNA construct using program O-005.
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.