Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Neuroscience Research Center of Changzheng Hospital, Second Military Medical University, Shanghai 200433, China.
J Cell Sci. 2011 Jan 15;124(Pt 2):186-97. doi: 10.1242/jcs.071357.
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 Ca(2+) 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 Ca(2+)-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 Ca(2+) and cofilin signaling during Slit-2-triggered repulsion.
嗅鞘细胞（OEC）在发育过程中从嗅上皮迁移到嗅球。然而，OEC 迁移的导向机制仍然是一个谜。在这里，我们发现迁移的 OEC 表达了排斥性导向因子 Slit-2 的受体。培养的 OEC 前的 Slit-2 梯度首先导致前沿的崩溃，然后导致细胞迁移的逆转。这些 Slit-2 作用取决于通过肌醇（1,4,5）-三磷酸受体通道从内部储存中释放 Ca2+。有趣的是，响应于 Slit-2 刺激，前沿的崩溃需要以 Ca2+依赖的方式激活 F-肌动蛋白切断蛋白 cofilin，而随后的体迁移的逆转则取决于 RhoA 活性在细胞中的逆转。最后，Slit-2 诱导的细胞迁移排斥作用可通过应用 F-肌动蛋白聚合和 RhoA 激酶抑制剂来完全模拟。我们的研究结果表明 Slit-2 是 OEC 迁移的一种排斥性导向因子，以及在 Slit-2 触发的排斥反应中 Ca2+和 cofilin 信号之间的意外联系。
