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标题：SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells
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作者：Mourad Ferdaoussi ; Jianyang Fu ; Xiaoqing Dai 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
DOI：10.1038/s41598-017-00344-z
语种：English
出版社：Springer Nature
摘要：Insulin secretion from pancreatic ß cells is a multistep process that requires the coordination of exocytotic proteins that integrate diverse signals. These include signals derived from metabolic control of post-translational SUMOylation and depolarization-induced rises in intracellular Ca(2+). Here we show that tomosyn, which suppresses insulin exocytosis by binding syntaxin1A, does so in a manner which requires its SUMOylation. Glucose-dependent de-SUMOylation of tomosyn1 at K298 releases syntaxin1A and controls the amplification of exocytosis in concert with a recently-identified tomosyn1-interacting partner; the Ca(2+)-binding protein secretagogin, which dissociates from tomosyn1 in response to Ca(2+)-raising stimuli and is required for insulin granule trafficking and exocytosis downstream of Ca(2+) influx. Together our results suggest that tomosyn acts as a key signaling hub in insulin secretion by integrating signals mediated by metabolism-dependent de-SUMOylation and electrically-induced entry of Ca(2+) to regulate the availability of exocytotic proteins required for the amplification of insulin secretion.