Slit-2 repels the migration of olfactory ensheathing cells by triggering Ca2+-dependent cofilin activation and RhoA inhibition
Slit-2 repels the migration of olfactory ensheathing cells by triggering Ca2+-dependent cofilin activation and RhoA inhibition
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DOI：
10.1242/jcs.071357
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发表时间：
2011-01-15
影响因子：
4
通讯作者：
He, Cheng
中科院分区：
文献类型：
--
作者：
Huang, Zhi-hui;Wang, Ying;He, Cheng
嗅鞘细胞（OEC）在发育过程中从嗅上皮迁移到嗅球。然而，OEC迁移的引导机制仍然是个谜。在这里，我们证明迁移的 OEC 表达排斥引导因子 Slit-2 的受体。培养的 OEC 前面的 Slit-2 梯度首先导致前导前沿崩溃，然后导致细胞迁移逆转。这些 Slit-2 效应取决于内部储存的 Ca2+ 通过肌醇 (1,4,5)-三磷酸受体通道的释放。有趣的是，响应 Slit-2 刺激，前导前沿的崩溃需要以 Ca2+ 依赖性方式激活 F-肌动蛋白切割蛋白丝切蛋白，而随后体细胞迁移的逆转取决于细胞内 RhoA 活性的逆转。最后，通过共同应用 F-肌动蛋白聚合抑制剂和 RhoA 激酶，完全模拟了 Slit-2 诱导的细胞迁移排斥。我们的研究结果表明，Slit-2 是 OEC 迁移的排斥引导因子，并且在 Slit-2 触发的排斥过程中，Ca2+ 和丝切蛋白信号传导之间存在意想不到的联系。
Olfactory ensheathing cells (OECs) migrate from the olfactory epithelium towards the olfactory bulb during development. However, the guidance mechanism for OEC migration remains a mystery. Here we show that migrating OECs expressed the receptor of the repulsive guidance factor Slit-2. A gradient of Slit-2 in front of cultured OECs first caused the collapse of the leading front, then the reversal of cell migration. These Slit-2 effects depended on the Ca2+ release from internal stores through inositol (1,4,5)-triphosphate receptor channels. Interestingly, in response to Slit-2 stimulation, collapse of the leading front required the activation of the F-actin severing protein cofilin in a Ca2+-dependent manner, whereas the subsequent reversal of the soma migration depended on the reversal of RhoA activity across the cell. Finally, the Slit-2-induced repulsion of cell migration was fully mimicked by co-application of inhibitors of F-actin polymerization and RhoA kinase. Our findings revealed Slit-2 as a repulsive guidance factor for OEC migration and an unexpected link between Ca2+ and cofilin signaling during Slit-2-triggered repulsion.