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

Cell | Apr 20, 2001

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 RIS Download

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

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Associated grants

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

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