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.
Publication types
-
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.
MeSH terms
-
Actins / metabolism
-
Amino Acid Sequence
-
Animals
-
Brain Chemistry
-
Cells, Cultured
-
Cloning, Molecular
-
Embryo, Mammalian / physiology*
-
Ephrin-A1
-
Eye / cytology
-
Fetal Proteins / metabolism*
-
Growth Cones / drug effects
-
Growth Cones / metabolism*
-
Guanine Nucleotide Exchange Factors / chemistry
-
Guanine Nucleotide Exchange Factors / genetics
-
Guanine Nucleotide Exchange Factors / metabolism*
-
Immunoblotting
-
In Situ Hybridization
-
Mice
-
Molecular Sequence Data
-
Nerve Tissue Proteins / metabolism*
-
Phylogeny
-
Protein Structure, Tertiary
-
Proteins / pharmacology
-
Rats
-
Receptor Protein-Tyrosine Kinases / metabolism*
-
Signal Transduction / physiology*
-
Two-Hybrid System Techniques
-
rho GTP-Binding Proteins / metabolism
Substances
-
Actins
-
Ephrin-A1
-
Fetal Proteins
-
Guanine Nucleotide Exchange Factors
-
Nerve Tissue Proteins
-
Ngef protein, mouse
-
Ngef protein, rat
-
Proteins
-
Receptor Protein-Tyrosine Kinases
-
rho GTP-Binding Proteins