ignaling through Arf6 guanine-nucleotide exchange factor cytohesin-1 regulates migration in Schwann cells
ignaling through Arf6 guanine-nucleotide exchange factor cytohesin-1 regulates migration in Schwann cells
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通过 Arf6 鸟嘌呤核苷酸交换因子 cytohesin-1 进行信号传导调节雪旺细胞的迁移
DOI：
10.1016/j.cellsig.2013.03.008
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
and Junji Yamauchi
中科院分区：
文献类型：
--
作者：
Yuki Miyamoto;Tomohiro Torii;Kazuaki Nakamura;Shou Takashima;Atsushi Sanbe;Akito Tanoue;and Junji Yamauchi
在周围神经系统（PNS）发育过程中，雪旺细胞在轴突髓鞘形成前沿神经元轴突迁移。虽然已经确定了雪旺细胞和周围神经元之间控制迁移的细胞间信号，但这些信号如何在细胞内转导到雪旺细胞中仍有待阐明。本研究表明，鸟嘌呤核苷酸交换因子（GEF）和效应因子Arf6是原代雪旺细胞迁移所必需的。在雪旺细胞中敲低细胞素-1或Arf6，以及用化学细胞素抑制剂SecinH3或敲除细胞素-1处理，可抑制周围神经元条件介质介导的迁移。条件培养基中含有的每一种生长因子刺激后也观察到类似的效果，这表明细胞染色素-1在神经元的可溶性配体信号转导中起作用。将小干扰（si） rna抗性的细胞素-1重新引入雪旺细胞，逆转了sirna转染的雪旺细胞的钝化迁移，说明了细胞素-1在迁移中的重要性。另一方面，引入含有Tyr-382突变的细胞分裂素-1，这是一种对其激活很重要的氨基酸，未能逆转原代雪旺细胞迁移的减少。这些结果表明，通过cytohesin-1的信号传导是雪旺细胞迁移所必需的，揭示了雪旺细胞迁移的新机制。
During development of the peripheral nervous system (PNS), Schwann cells migrate along neuronal axons before initiating myelination of the axons. While intercellular signals controlling migration, between Schwann cells and peripheral neurons, are established, how their intracellular transduction of the signals into Schwann cells still remains to be clarified. Here, we show that cytohesin-1, a guanine-nucleotide exchange factor (GEF), and the effector Arf6 are required for migration of primary Schwann cells. Knockdown of cytohesin-1 or Arf6 in Schwann cells, as well as treatment with the chemical cytohesin inhibitor SecinH3 or knockout of cytohesin-1, inhibits peripheral neuronal conditioned medium-mediated migration. Similar effects are also observed following stimulation with each of growth factors contained in a conditioned medium, suggesting that cytohesin-1 plays a role in transducing soluble ligand signals from neurons. Reintroduction of small interfering (si)RNA-resistant cytohesin-1 into Schwann cells reverses blunted migration in the siRNA-transfected Schwann cells, illustrating the importance of cytohesin-1 in migration. On the other hand, introduction of cytohesin-1 that harbors the Tyr-382 mutation, which is an amino acid that is important for its activation, failed to reverse the reduction in primary Schwann cell migration. These results suggest that signaling through cytohesin-1 is required for Schwann cell migration, revealing a novel mechanism for Schwann cell migration.