The netrin receptor UNC-40/DCC stimulates axon attraction and outgrowth through enabled and, in parallel, Rac and UNC-115/abLIM

Zemer Gitai, Timothy W. Yu, Erik A. Lundquist, Marc Tessier-Lavigne, Cornelia I. Bargmann

Research output: Contribution to journalArticlepeer-review

180 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)53-65
Number of pages13
JournalNeuron
Volume37
Issue number1
DOIs
StatePublished - Jan 9 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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