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