Author/Authors :
Steven M. Shamah، نويسنده , , Michael Z. Lin، نويسنده , , Jeffrey L. Goldberg، نويسنده , , Soline Estrach، نويسنده , , Mustafa Sahin، نويسنده , , Linda Hu، نويسنده , , Mihaela Bazalakova، نويسنده , , Rachel L. Neve، نويسنده , , Gabriel Corfas، نويسنده , , Anne Debant، نويسنده , , Michael E. Greenberg، نويسنده ,
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.