Neurotrophin 3 activation of TrkC induces Schwann cell migration through the c-Jun N-terminal kinase pathway
Neurotrophin 3 activation of TrkC induces Schwann cell migration through the c-Jun N-terminal kinase pathway
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DOI：
10.1073/pnas.2336152100
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发表时间：
2003-11-25
影响因子：
11.1
通讯作者：
Shooter, EM
中科院分区：
文献类型：
--
作者：
Yamauchi, J;Chan, JR;Shooter, EM
在神经发育和损伤过程中，神经胶质细胞和神经元之间复杂的相互作用对于神经功能的建立至关重要。神经营养因子在神经系统发育过程中发挥多种作用，包括细胞存活、生长和分化。在这里，我们发现从坐骨神经分离的雪旺细胞的迁移被神经营养因子3显著增强，而不是被神经生长因子或脑源性神经营养因子增强。从p（75NTR-/-）小鼠坐骨神经分离的雪旺细胞中也观察到神经营养因子-3诱导的细胞迁移，表明神经营养因子3通过TrkC促进细胞迁移。这种作用被Trk受体家族的抑制剂K252a阻断。此外，神经营养因子-3诱导的细胞迁移依赖于Rho GTPases （Rac1和Cdc42）和c-Jun n-末端激酶。我们在表达TrkC的Cos-7细胞中获得了相同的结果。综上所述，这些结果表明TrkC的神经营养因子3激活通过c-Jun n末端激酶信号通路诱导雪旺细胞迁移。
During development and nerve injury, complex interactions between glial cells and neurons are essential for establishing proper nerve function. Neurotrophins play multiple roles in the developing nervous system, including cell survival, growth, and differentiation. Here we show that migration of Schwann cells, isolated from sciatic nerves, is significantly enhanced by neurotrophin 3, but not by nerve growth factor or brain-derived neurotrophic factor. The neurotrophin-3-induced cell migration was also observed in Schwann cells isolated from sciatic nerves of p(75NTR-/-) mice, indicating that neurotrophin 3 enhances cell migration through TrkC. This effect was blocked by K252a, an inhibitor of the Trk receptor family. Additionally, the neurotrophin-3-induced cell migration depended on Rho GTPases (Rac1 and Cdc42) and c-Jun N-terminal kinase. We obtained the same results with Cos-7 cells expressing TrkC. Taken together, these results suggest that neurotrophin 3 activation of TrkC induces Schwann cell migration through the c-Jun N-terminal kinase signaling pathway.