Nature Neuroscience
7, 1204 - 1212 (2004)
Published online: 17 October 2004; | doi:10.1038/nn1330
Focal adhesion kinase in netrin-1 signalingXiu-rong Ren1, 6, Guo-li Ming2, 6, Yi Xie1, 6, Yan Hong1, Dong-mei Sun1, Zhong-qiu Zhao3, Zhu Feng1, 4, Qiang Wang1, 4, 5, Sangwoo Shim2, Zhou-feng Chen3, Hong-jun Song2, Lin Mei1, 4, 5
& Wen-cheng Xiong1, 41
Department of Pathology, University of Alabama, Birmingham, Alabama 35294, USA. 2
Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. 3
Departments of Anesthesiology, Psychiatry, Molecular Biology and Pharmacology, School of Medicine Pain Center, Washington University, St. Louis, Missouri 63110, USA. 4
Department of Neurology and Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912, USA. 5
Departments of Neurobiology, Physical Medicine and Rehabilitation, University of Alabama, Birmingham, Alabama 35294, USA. 6
These authors contributed equally to this work.
Correspondence should be addressed to Wen-cheng Xiong wxiong@mcg.eduNetrins are a family of secreted molecules that are important for axonal outgrowth and guidance in the developing nervous system. However, the signaling mechanisms that lie immediately downstream of netrin receptors remain poorly understood. Here we report that the netrin receptor DCC (deleted in colorectal cancer) interacts with the focal adhesion kinase (FAK), a kinase implicated in regulating cell adhesion and migration. FAK was expressed in developing brains and was localized with DCC in cultured neurons. Netrin-1 induced FAK and DCC tyrosine phosphorylation. Disruption of FAK signaling abolished netrin-1-induced neurite outgrowth and attractive growth cone turning. Taken together, these results indicate a new signaling mechanism for DCC, in which FAK is activated upon netrin-1 stimulation and mediates netrin-1 function; they also identify a critical role for FAK in axon navigation.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
