Contact-induced clustering of syntaxin and munc18 docks secretory granules at the exocytosis site
Contact-induced clustering of syntaxin and munc18 docks secretory granules at the exocytosis site
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DOI：
10.1038/ncomms4914
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发表时间：
2014-05-01
影响因子：
16.6
通讯作者：
Barg, Sebastian
中科院分区：
文献类型：
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作者：
Gandasi, Nikhil R.;Barg, Sebastian
分泌囊泡在质膜上的对接是胞吐作用的先决条件。目前的模型提出筏状集群含有突触融合蛋白作为对接受体，但这是缺乏直接的证据。在这里，我们提供了几个胞吐蛋白（突触融合蛋白，SNAP 25，munc 18，munc 13和rab 3）在胰岛素颗粒释放网站的定量测量，并显示对接符合快速从头形成突触融合蛋白1/munc 18集群在新生的对接网站。这种簇的形成防止了脱离，并且在失败的对接尝试期间没有观察到。过表达的突触融合蛋白的N-末端Habc结构域竞争性干扰集群的形成和成功的对接。SNAP 25和munc 13在一分钟后被招募到对接位点，这与munc 13在颗粒引发而不是对接中的作用一致。我们的结论是，分泌囊泡码头诱导syntaxin 1/munc 18集群在靶膜，并没有发现预先形成的对接受体的证据。
Docking of secretory vesicles at the plasma membrane is a poorly understood prerequisite for exocytosis. Current models propose raft-like clusters containing syntaxin as docking receptor, but direct evidence for this is lacking. Here we provide quantitative measurements of several exocytosis proteins (syntaxin, SNAP25, munc18, munc13 and rab3) at the insulin granule release site and show that docking coincides with rapid de novo formation of syntaxin1/munc18 clusters at the nascent docking site. Formation of such clusters prevents undocking and is not observed during failed docking attempts. Overexpression of syntaxins' N-terminal Habc-domain competitively interferes with both cluster formation and successful docking. SNAP25 and munc13 are recruited to the docking site more than a minute later, consistent with munc13's reported role in granule priming rather than docking. We conclude that secretory vesicles dock by inducing syntaxin1/munc18 clustering in the target membrane, and find no evidence for preformed docking receptors.