title: EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin.
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.
authors.affiliation: Division of Neuroscience, Children's Hospital and the Department of Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Shamah
authors.forename: M Z
authors.initials: MZ
authors.lastname: Lin
authors.forename: J L
authors.initials: JL
authors.lastname: Goldberg
authors.forename: S
authors.initials: S
authors.lastname: Estrach
authors.forename: M
authors.initials: M
authors.lastname: Sahin
authors.forename: L
authors.initials: L
authors.lastname: Hu
authors.forename: M
authors.initials: M
authors.lastname: Bazalakova
authors.forename: R L
authors.initials: RL
authors.lastname: Neve
authors.forename: G
authors.initials: G
authors.lastname: Corfas
authors.forename: A
authors.initials: A
authors.lastname: Debant
authors.forename: M E
authors.initials: ME
authors.lastname: Greenberg
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004622:Embryo, Mammalian / Q000502:physiology*; D036382:Ephrin-A1; D005123:Eye / Q000166:cytology; D005326:Fetal Proteins / Q000378:metabolism*; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D036382:Ephrin-A1; D005326:Fetal Proteins; D020662:Guanine Nucleotide Exchange Factors; D009419:Nerve Tissue Proteins; C504479:Ngef protein, mouse; C504480:Ngef protein, rat; D011506:Proteins; D020794:Receptor Protein-Tyrosine Kinases; D020741:rho GTP-Binding Proteins