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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.

Titel:	EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin.
Autor/in / Beteiligte Person:	Shamah, SM ; Lin, MZ ; Goldberg, JL ; Estrach, S ; Sahin, M ; Hu, L ; Bazalakova, M ; Neve, RL ; Corfas, G ; Debant, A ; Greenberg, ME
Link:	Full Text Finder (Volltext)
Zeitschrift:	Cell, Jg. 105 (2001-04-20), Heft 2, S. 233-44
Veröffentlichung:	Cambridge, Ma : Cell Press ; <i>Original Publication</i>: Cambridge, MIT Press., 2001
Medientyp:	academicJournal
ISSN:	0092-8674 (print)
DOI:	10.1016/s0092-8674(01)00314-2
Schlagwort:	Actins metabolism Amino Acid Sequence Animals Brain Chemistry Cells, Cultured Cloning, Molecular Ephrin-A1 Eye cytology Growth Cones drug effects Guanine Nucleotide Exchange Factors chemistry Guanine Nucleotide Exchange Factors genetics Immunoblotting In Situ Hybridization Mice Molecular Sequence Data Phylogeny Protein Structure, Tertiary Proteins pharmacology Rats Two-Hybrid System Techniques rho GTP-Binding Proteins metabolism Embryo, Mammalian physiology Fetal Proteins metabolism Growth Cones metabolism Guanine Nucleotide Exchange Factors metabolism Nerve Tissue Proteins metabolism Receptor Protein-Tyrosine Kinases metabolism Signal Transduction physiology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. Language: English [Cell] 2001 Apr 20; Vol. 105 (2), pp. 233-44. MeSH Terms: Embryo, Mammalian / physiology ; Fetal Proteins / metabolism ; Growth Cones / metabolism ; Guanine Nucleotide Exchange Factors / metabolism ; Nerve Tissue Proteins / metabolism ; Receptor Protein-Tyrosine Kinases / metabolism ; Signal Transduction / *physiology ; Actins / metabolism ; Amino Acid Sequence ; Animals ; Brain Chemistry ; Cells, Cultured ; Cloning, Molecular ; Ephrin-A1 ; Eye / cytology ; Growth Cones / drug effects ; Guanine Nucleotide Exchange Factors / chemistry ; Guanine Nucleotide Exchange Factors / genetics ; Immunoblotting ; In Situ Hybridization ; Mice ; Molecular Sequence Data ; Phylogeny ; Protein Structure, Tertiary ; Proteins / pharmacology ; Rats ; Two-Hybrid System Techniques ; rho GTP-Binding Proteins / metabolism Grant Information: R01 EY11310 United States EY NEI NIH HHS; R01 NS35884 United States NS NINDS NIH HHS; NS10070-02 United States NS NINDS NIH HHS; R01 NS045500 United States NS NINDS NIH HHS; HD18655 United States HD NICHD NIH HHS; CA43855 United States CA NCI NIH HHS; 1K08HD01384 United States HD NICHD NIH HHS Substance Nomenclature: 0 (Actins) ; 0 (Ephrin-A1) ; 0 (Fetal Proteins) ; 0 (Guanine Nucleotide Exchange Factors) ; 0 (Nerve Tissue Proteins) ; 0 (Ngef protein, mouse) ; 0 (Ngef protein, rat) ; 0 (Proteins) ; EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) ; EC 3.6.5.2 (rho GTP-Binding Proteins) Entry Date(s): Date Created: 20010505 Date Completed: 20010531 Latest Revision: 20220224 Update Code: 20240513

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