Neurotrophins regulate Schwann cell migration by activating divergent signaling pathways dependent on Rho GTPases.
Neurotrophins are recognized widely as essential factors in the developing nervous system. Previously, we demonstrated that neurotrophin 3 activation of TrkC inhibits Schwann cell myelination and enhances the migration of primary Schwann cells through the signaling pathway regulated by the Rho GTPases Rac1 and Cdc42. Here, we show that neurotrophins activate divergent signaling pathways to promote or inhibit Schwann cell migration. Endogenous brain-derived neurotrophic factor acting through p75(NTR) inhibits Schwann cell migration dramatically by Src kinase-dependent activation of the guanine-nucleotide exchange factor Vav2 and RhoA. Together, these results suggest that neurotrophins and their receptors differentially regulate Schwann cell migration through the signaling pathways that depend on Rho GTPases.
Yamauchi
Junji
J
Department of Neurobiology, Stanford University School of Medicine, 299 Campus Drive, Stanford, CA 94305-5125, USA.
Chan
Jonah R
JR
Shooter
Eric M
EM
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D051379:Mice; D009414:Nerve Growth Factors / Q000502:physiology*; D020933:Neurotrophin 3 / Q000494:pharmacology / Q000502:physiology; D015513:Oncogene Proteins / Q000502:physiology; D051567:Proto-Oncogene Proteins c-vav; D051381:Rats; D020800:Receptor, Nerve Growth Factor; D020813:Receptor, trkB / Q000502:physiology; D020812:Receptor, trkC / Q000502:physiology; D017475:Receptors, Nerve Growth Factor / Q000502:physiology; D012583:Schwann Cells / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000502:physiology; D019061:src-Family Kinases / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D015513:Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; C490565:Vav2 protein, mouse; C490564:Vav2 protein, rat; D020813:Receptor, trkB; D020812:Receptor, trkC; D019061:src-Family Kinases; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein