title: 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 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.
authors.affiliation: Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Guofa
authors.initials: G
authors.lastname: Liu
authors.forename: Weiquan
authors.initials: W
authors.lastname: Li
authors.forename: Xue
authors.initials: X
authors.lastname: Gao
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.forename: Claudia
authors.initials: C
authors.lastname: Jürgensen
authors.forename: Hwan-Tae
authors.initials: HT
authors.lastname: Park
authors.forename: Nah-Young
authors.initials: NY
authors.lastname: Shin
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.forename: Ming-Liang
authors.initials: ML
authors.lastname: He
authors.forename: Steven K
authors.initials: SK
authors.lastname: Hanks
authors.forename: Jane Y
authors.initials: JY
authors.lastname: Wu
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Guan
authors.forename: Yi
authors.initials: Y
authors.lastname: Rao
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D002642:Chick Embryo; D050719:Crk-Associated Substrate Protein / Q000502:physiology*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D009414:Nerve Growth Factors / Q000502:physiology*; D000075388:Netrin-1; D011247:Pregnancy; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000502:physiology
chemical_list: D050719:Crk-Associated Substrate Protein; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D020830:rac1 GTP-Binding Protein