CGC Bibliography Paper 5719

The netrin receptor UNC-40/DCC stimulates axon attraction and outgrowth through Enabled and, in parallel, Rac and UNC-115/AbLIM.

Gitai Z, Yu TW, Lundquist EA, Tessier-Lavigne M, Bargmann CI

Medline:

12526772

Citation:

Neuron 37: 53-65 2003

Type:

ARTICLE

Genes:

ced-10 mig-2 sax-3 slt-1 unc-5 unc-6 unc-34 unc-40 unc-44 unc-51 unc-60 unc-73 unc-76 unc-115 vab-1

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.