Insulin Stimulates Syntaxin4 SNARE Complex Assembly via a Novel Regulatory Mechanism
Insulin Stimulates Syntaxin4 SNARE Complex Assembly via a Novel Regulatory Mechanism
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DOI：
10.1128/mcb.01203-13
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发表时间：
2014-04-01
影响因子：
5.3
通讯作者：
Bryant, Nia J.
中科院分区：
文献类型：
--
作者：
Kioumourtzoglou, Dimitrios;Gould, Gwyn W.;Bryant, Nia J.
胰岛素通过增加GLUT4易化葡萄糖转运体的胞外转运速率，促进葡萄糖从细胞内储存到质膜，从而刺激葡萄糖向脂肪和肌肉细胞的转运。GLUT4向质膜的转运是通过形成含有Synaxin4、SNAP23和VAMP2的功能性SNAR复合体来实现的。在这里，我们使用了原位邻近连接试验来整合这两个观察结果，首次证明了胰岛素刺激导致脂肪细胞中含有合成素4的SNARE复合体的形成增加。此外，我们证明，胰岛素通过动员在基础条件下处于不活跃状态的Synaxin4池来增加SNARE复合体的形成。最后，我们已经确定调节蛋白Munc18c的磷酸化是协调这一过程的分子开关，Munc18c是胰岛素受体的直接靶标。因此，这份报告提供了细胞如何改变膜运输的分子细节，以响应外部刺激，在这种情况下，胰岛素。
Insulin stimulates glucose transport into fat and muscle cells by increasing the exocytic trafficking rate of the GLUT4 facilitative glucose transporter from intracellular stores to the plasma membrane. Delivery of GLUT4 to the plasma membrane is mediated by formation of functional SNARE complexes containing syntaxin4, SNAP23, and VAMP2. Here we have used an in situ proximity ligation assay to integrate these two observations by demonstrating for the first time that insulin stimulation causes an increase in syntaxin4-containing SNARE complex formation in adipocytes. Furthermore, we demonstrate that insulin brings about this increase in SNARE complex formation by mobilizing a pool of syntaxin4 held in an inactive state under basal conditions. Finally, we have identified phosphorylation of the regulatory protein Munc18c, a direct target of the insulin receptor, as a molecular switch to coordinate this process. Hence, this report provides molecular detail of how the cell alters membrane traffic in response to an external stimulus, in this case, insulin.