Ras activation of a Rac1 exchange factor, Tiam1, mediates neurotrophin-3-induced Schwann cell migration

被引:87
作者
Yamauchi, J
Miyamoto, Y
Tanoue, A
Shooter, EM
Chan, JR
机构
[1] Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA
[2] Natl Res Inst Child Hlth & Dev, Dept Pharmacol, Setagaya Ku, Tokyo 1578535, Japan
[3] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Cell & Neurobiol, Los Angeles, CA 90089 USA
关键词
small GTPase; TrkC;
D O I
10.1073/pnas.0507125102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Endogenous neurotrophins positively and negatively regulate migration of premyelinating Schwann cells before the initiation of myelination. Neurotrophin-3 (NT3) acting through the TrkC receptor tyrosine kinase stimulates Schwann cell migration via the Rho GTPases Rac1 and Cdc42. We previously demonstrated that TrkC directly phosphorylates and activates Dbs, the guanine-nucleotide exchange factor (GEF) for Cdc42, to partially mediate Schwann cell migration. Here, we identify T lymphoma invasion and metastasis (Tiam) 1 as the Rac1-specific guanine-nucleotide exchange factor involved in NT3-induced Schwann cell migration. Furthermore, the interaction between the small GTPase Ras and Tiam1 plays an essential role in the activation of Rac1. Taken together, these results suggest that NT3 activation of TrkC stimulates Schwann cell migration through two parallel signaling units, Ras/Tiam1/Rac1 and Dbs/Cdc42, and that Schwann cell migration is uniquely regulated in the case of Ras and Rac1, by two different types of small GTPases.
引用
收藏
页码:14889 / 14894
页数:6
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