Plexin B mediates axon guidance in Drosophila by simultaneously inhibiting active Rac and enhancing RhoA signaling

Neuron. 2001 Oct 11;32(1):39-51. doi: 10.1016/s0896-6273(01)00453-6.

Abstract

Plexins are neuronal receptors for the repulsive axon guidance molecule Semaphorins. Previous studies showed that Plexin B (PlexB) binds directly to the active, GTP-bound form of the Rac GTPase. Here, we define a seven amino acid sequence in PlexB required for Rac(GTP) binding. The interaction of PlexB with Rac(GTP) is necessary for Plexin-mediated axon guidance in vivo. A different region of PlexB binds to RhoA. Dosage-sensitive genetic interactions suggest that PlexB suppresses Rac activity and enhances RhoA activity. Biochemical evidence indicates that PlexB sequesters Rac(GTP) from its downstream effector PAK. These results suggest a model whereby PlexB mediates repulsion by coordinately regulating two small GTPases in opposite directions: PlexB binds to Rac(GTP) and downregulates its output by blocking its access to PAK and, at the same time, binds to and increases the output of RhoA.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Axons / enzymology*
  • Binding Sites / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Consensus Sequence
  • Drosophila
  • Drosophila Proteins*
  • Gene Expression / physiology
  • Molecular Sequence Data
  • Nerve Tissue Proteins / metabolism*
  • Phenotype
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptors, Cell Surface / metabolism*
  • Semaphorins*
  • Signal Transduction / physiology*
  • p21-Activated Kinases
  • rac GTP-Binding Proteins / antagonists & inhibitors*
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Cell Adhesion Molecules, Neuronal
  • Drosophila Proteins
  • Nerve Tissue Proteins
  • Receptors, Cell Surface
  • Semaphorins
  • plexB protein, Drosophila
  • Pak protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • p21-Activated Kinases
  • rac GTP-Binding Proteins
  • rhoA GTP-Binding Protein