EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin |
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Authors: | Shamah S M Lin M Z Goldberg J L Estrach S Sahin M Hu L Bazalakova M Neve R L Corfas G Debant A Greenberg M E |
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Affiliation: | Division of Neuroscience, Children's Hospital and the Department of Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. |
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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. |
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