Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway

Cell. 2001 Oct 19;107(2):209-21. doi: 10.1016/s0092-8674(01)00530-x.

Abstract

The Slit protein guides neuronal and leukocyte migration through the transmembrane receptor Roundabout (Robo). We report here that the intracellular domain of Robo interacts with a novel family of Rho GTPase activating proteins (GAPs). Two of the Slit-Robo GAPs (srGAPs) are expressed in regions responsive to Slit. Slit increased srGAP1-Robo1 interaction and inactivated Cdc42. A dominant negative srGAP1 blocked Slit inactivation of Cdc42 and Slit repulsion of migratory cells from the anterior subventricular zone (SVZa) of the forebrain. A constitutively active Cdc42 blocked the repulsive effect of Slit. These results have demonstrated important roles for GAPs and Cdc42 in neuronal migration. We propose a signal transduction pathway from the extracellular guidance cue to intracellular actin polymerization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Amino Acid Sequence
  • Blotting, Northern
  • Cell Line
  • Cell Membrane / metabolism
  • Cell Movement*
  • Drosophila Proteins*
  • GTP Phosphohydrolases / metabolism*
  • Genes, Dominant
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Mutation
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology*
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Messenger / metabolism
  • Receptors, Immunologic / metabolism*
  • Retroviridae / genetics
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Tissue Distribution
  • Two-Hybrid System Techniques
  • cdc42 GTP-Binding Protein / metabolism*

Substances

  • Actins
  • Drosophila Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Receptors, Immunologic
  • roundabout protein
  • sli protein, Drosophila
  • GTP Phosphohydrolases
  • cdc42 GTP-Binding Protein

Associated data

  • GENBANK/AY057898
  • GENBANK/AY057899
  • GENBANK/AY057900