EphA Receptors Regulate Growth Cone Dynamics Through the Novel Guanine Nucleotide Exchange Factor Ephexin

Cell. 2001 Apr 20;105(2):233-44. doi: 10.1016/s0092-8674(01)00314-2.

Abstract

Eph receptors transduce short-range repulsive signals for axon guidance by modulating actin dynamics within growth cones. We report the cloning and characterization of ephexin, a novel Eph receptor-interacting protein that is a member of the Dbl family of guanine nucleotide exchange factors (GEFs) for Rho GTPases. Ephrin-A stimulation of EphA receptors modulates the activity of ephexin leading to RhoA activation, Cdc42 and Rac1 inhibition, and cell morphology changes. In addition, expression of a mutant form of ephexin in primary neurons interferes with ephrin-A-induced growth cone collapse. The association of ephexin with Eph receptors constitutes a molecular link between Eph receptors and the actin cytoskeleton and provides a novel mechanism for achieving highly localized regulation of growth cone motility.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Amino Acid Sequence
  • Animals
  • Brain Chemistry
  • Cells, Cultured
  • Cloning, Molecular
  • Embryo, Mammalian / physiology*
  • Ephrin-A1
  • Eye / cytology
  • Fetal Proteins / metabolism*
  • Growth Cones / drug effects
  • Growth Cones / metabolism*
  • Guanine Nucleotide Exchange Factors / chemistry
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Immunoblotting
  • In Situ Hybridization
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins / metabolism*
  • Phylogeny
  • Protein Structure, Tertiary
  • Proteins / pharmacology
  • Rats
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction / physiology*
  • Two-Hybrid System Techniques
  • rho GTP-Binding Proteins / metabolism

Substances

  • Actins
  • Ephrin-A1
  • Fetal Proteins
  • Guanine Nucleotide Exchange Factors
  • Nerve Tissue Proteins
  • Ngef protein, mouse
  • Ngef protein, rat
  • Proteins
  • Receptor Protein-Tyrosine Kinases
  • rho GTP-Binding Proteins