Neurotrophins regulate Schwann cell migration by activating divergent signaling pathways dependent on Rho GTPases

• DOI: 10.1073/pnas.0402795101
• Publication Date: 2004-05-26T00:43:14Z
• Authors: Junji Yamauchi; Jonah R. Chan; Eric M. Shooter
• Keywords: Oncogene Proteins; rho GTP-Binding Proteins; 0301 basic medicine; Brain-Derived Neurotrophic Factor; Receptors, Nerve Growth Factor; Receptor, Nerve Growth Factor; Rats; Enzyme Activation; Mice; 03 medical and health sciences; src-Family Kinases; Neurotrophin 3; Cell Movement; Animals; Receptor, trkB; Receptor, trkC; Nerve Growth Factors; Schwann Cells; Proto-Oncogene Proteins c-vav; rhoA GTP-Binding Protein; Cells, Cultured; Signal Transduction

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.