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

Neuron. 2003 Jan 9;37(1):53-65. doi: 10.1016/s0896-6273(02)01149-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / genetics
  • Actin Cytoskeleton / metabolism
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Communication / physiology*
  • Cell Differentiation / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Genes, Suppressor / physiology
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Mutation / genetics
  • Nervous System / cytology
  • Nervous System / embryology*
  • Nervous System / metabolism
  • Nervous System Malformations / genetics
  • Nervous System Malformations / pathology
  • Netrin Receptors
  • Phenotype
  • Promoter Regions, Genetic / genetics
  • Protein Structure, Tertiary / genetics
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Recombinant Fusion Proteins
  • Signal Transduction / genetics*
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism

Substances

  • CED-10 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Cell Adhesion Molecules
  • DNA-Binding Proteins
  • ENA-VASP proteins
  • Microfilament Proteins
  • Netrin Receptors
  • Receptors, Cell Surface
  • Recombinant Fusion Proteins
  • UNC-115 protein, C elegans
  • UNC-40 protein, C elegans
  • rac GTP-Binding Proteins