Control of plasma membrane lipid homeostasis by the extended synaptotagmins.
Control of plasma membrane lipid homeostasis by the extended synaptotagmins.
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DOI：
10.1038/ncb3339
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发表时间：
2016-05
影响因子：
21.3
通讯作者：
De Camilli P
中科院分区：
文献类型：
--
作者：
Saheki Y;Bian X;Schauder CM;Sawaki Y;Surma MA;Klose C;Pincet F;Reinisch KM;De Camilli P
质膜（PM）脂质的急性代谢变化，如介导信号传导反应的脂质，可通过稳态反应迅速补偿，其分子基础知之甚少。在这里，我们表明，扩展突触结合蛋白（E-Syts），ER蛋白作为PI（4，5）P2和Ca 2+调节的系链到PM，参与这些反应。E-Syts在体外双层之间转移甘油脂，这种转移需要Ca 2+和它们的SMP结构域，一种脂质携带模块。缺乏E-Syts的基因组编辑的细胞在静止时不表现出主要甘油脂的异常，但在通过PLC活化的PI（4，5）P2水解后显示PM二酰基甘油（DAG）的增强和持续积累，这可以通过表达E-Syt 1而不是通过缺乏SMP结构域的突变体E-Syt 1来拯救。响应于切割PI（4，5）P2和升高Ca 2+的刺激而形成E-Syts依赖性ER-PM系链可以通过将其转移到ER进行代谢再循环来帮助逆转PM中DAG的积累。
Acute metabolic changes of plasma membrane (PM) lipids, such as those mediating signaling reactions, are rapidly compensated by homeostatic responses whose molecular basis is poorly understood. Here we show that the Extended-Synaptotagmins (E-Syts), ER proteins which function as PI(4,5)P2 and Ca2+-regulated tethers to the PM, participate in these responses. E-Syts transfer glycerolipids between bilayers in vitro and such transfer requires Ca2+ and their SMP domain, a lipid-harboring module. Genome edited cells lacking E-Syts do not exhibit abnormalities in the major glycerolipids at rest, but display enhanced and sustained accumulation of PM diacylglycerol (DAG) upon PI(4,5)P2 hydrolysis by PLC activation, which can be rescued by expression of E-Syt1, but not by mutant E-Syt1 lacking the SMP domain. The formation of E-Syts-dependent ER-PM tethers in response to stimuli that cleave PI(4,5)P2 and elevate Ca2+ may help reverse accumulation of DAG in the PM by transferring it to the ER for metabolic recycling.