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EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin.

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.

Pubmed ID: 11336673

Authors

  • Shamah SM
  • Lin MZ
  • Goldberg JL
  • Estrach S
  • Sahin M
  • Hu L
  • Bazalakova M
  • Neve RL
  • Corfas G
  • Debant A
  • Greenberg ME

Journal

Cell

Publication Data

April 20, 2001

Associated Grants

  • Agency: NICHD NIH HHS, Id: 1K08HD01384
  • Agency: NCI NIH HHS, Id: CA43855
  • Agency: NICHD NIH HHS, Id: HD18655
  • Agency: NINDS NIH HHS, Id: NS10070-02
  • Agency: NEI NIH HHS, Id: R01 EY11310
  • Agency: NINDS NIH HHS, Id: R01 NS045500
  • Agency: NINDS NIH HHS, Id: R01 NS35884

Mesh Terms

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