Netrins promote axon outgrowth and turning through DCC/UNC-40 receptors. To characterize Netrin signaling, we generated a gain-of-function UNC-40 molecule, MYR::UNC-40. MYR::UNC-40 causes axon guidance defects, excess axon branching, and excessive axon and cell body outgrowth. These defects are suppressed by loss-of-function mutations in ced-10 (a Rac GTPase), unc-34 (an Enabled homolog), and unc-115 (a putative actin binding protein). ced-10, unc-34, and unc-115 also function in endogenous unc-40 signaling. Our results indicate that Enabled functions in axonal attraction as well as axon repulsion. UNC-40 has two conserved cytoplasmic motifs that mediate distinct downstream pathways: CED-10, UNC-115, and the UNC-40 P2 motif act in one pathway, and UNC-34 and the UNC-40 P1 motif act in the other. Thus, UNC-40 might act as a scaffold to deliver several independent signals to the actin cytoskeleton.
Copyright © 2003 Cell Press.
Neuron, Vol 37, 53-65, 9 January 2003
Article
The Netrin Receptor UNC-40/DCC Stimulates Axon Attraction and Outgrowth through Enabled and, in Parallel, Rac and UNC-115/AbLIM
1Howard Hughes Medical Institute, Department of Anatomy, Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143 USA
2Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045 USA
3Howard Hughes Medical Institute, Department of Biological Sciences, Stanford University, Stanford, CA 94305 USA
Corresponding author
Marc Tessier-Lavigne
marctl@stanford.edu
Summary
Footnotes
*Correspondence: Cornelia I. Bargmann; e-mail: cori@itsa.ucsf.edu
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