Repulsive migration of schwann cells induced by slit‐2 through Ca2+‐dependent RhoA‐Myosin signaling
Repulsive migration of schwann cells induced by slit‐2 through Ca2+‐dependent RhoA‐Myosin signaling
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DOI：
10.1002/glia.22464
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发表时间：
2013-05
期刊：
影响因子：
6.2
通讯作者：
Ying Wang;H. Teng;Zhihui Huang
中科院分区：
文献类型：
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作者：
Ying Wang;H. Teng;Zhihui Huang
在发育过程中，雪旺细胞在开始髓鞘形成之前沿着轴突迁移，并且它们的迁移促进损伤后的周围神经再生。轴突导向分子Slit-2在外周发育和神经再生过程中高度表达;然而，Slit-2是否调节雪旺细胞的迁移仍然是一个谜。在这里，我们发现Slit-2受体Robo-1和Robo-2在体外和体内的雪旺细胞中高度表达。使用三种不同的迁移试验，我们发现Slit‐2排斥培养的雪旺细胞的迁移。此外，向迁移的雪旺细胞正面施加Slit-2梯度首先引起前缘的塌陷，然后逆转雪旺细胞的索马移位。Slit-2对雪旺细胞迁移的排斥作用依赖于内部储存的Ca 2+信号释放。有趣的是，响应于Slit-2刺激，前沿的崩溃需要F-肌动蛋白和局灶性粘附的损失，而随后的索马易位的逆转依赖于RhoA-Rock-肌球蛋白信号通路。综上所述，我们证明了Slit‐2以Ca 2+依赖性方式通过RhoA‐肌球蛋白信号通路排斥培养的许旺细胞的迁移。
Schwann cells migrate along axons before initiating myelination during development and their migration facilitates peripheral nerve regeneration after injury. Axon guidance molecule Slit‐2 is highly expressed during peripheral development and nerve regeneration; however, whether Slit‐2 regulates the migration of Schwann cells remains a mystery. Here we show that Slit‐2 receptor Robo‐1 and Robo‐2 were highly expressed in Schwann cells in vitro and in vivo. Using three distinct migration assays, we found that Slit‐2 repelled the migration of cultured Schwann cells. Furthermore, frontal application of a Slit‐2 gradient to migrating Schwann cells first caused the collapse of leading front, and then reversed soma translocation of Schwann cells. The repulsive effects of Slit‐2 on Schwann cell migration depended on a Ca2+ signaling release from internal stores. Interestingly, in response to Slit‐2 stimulation, the collapse of leading front required the loss of F‐actin and focal adhesion, whereas the subsequent reversal of soma translocation depended on RhoA‐Rock‐Myosin signaling pathways. Taken together, we demonstrate that Slit‐2 repels the migration of cultured Schwann cells through RhoA‐Myosin signaling pathways in a Ca2+‐dependent manner.