Polymodal Control of TMEM16x Channels and Scramblases.

Polymodal Control of TMEM16x Channels and Scramblases.
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DOI:
10.3390/ijms23031580
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发表时间:
2022-01-29
影响因子:
5.6
通讯作者:
Tammaro P
Tammaro P
中科院分区:
生物学2区
文献类型:
--
作者:
Agostinelli E;Tammaro P

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TMEM 16 A/Anoctamin-1钙激活氯离子通道(CaCC)有助于一系列重要功能,如控制血管张力和上皮离子转运。该通道是具有不同功能的10种蛋白质(TMEM 16 x)家族的创始成员;一些成员(即,TMEM 16 A和TMEM 16 B)充当CaCC,而其它是脂质扰码酶,联合收割机组合通道和扰码酶功能,或执行额外的细胞作用。TMEM 16 x蛋白通常由激动剂诱导的Ca 2+释放激活,所述Ca 2+释放由Gq蛋白偶联受体(GqPCR)激活引起;因此,TMEM 16 x蛋白将Ca 2+信号传导与细胞电活性和/或脂质转运联系起来。最近的研究表明,一系列其他细胞因子,包括质膜脂质,pH值,缺氧,ATP和辅助蛋白,也控制TMEM 16 A通道及其旁系同源物的活性,这表明TMEM 16 x蛋白是有效的多模态传感器的细胞内稳态。在这里,我们审查的分子病理生理学,结构生物学,和多种细胞因子的调节TMEM 16 x蛋白的机制。
The TMEM16A/anoctamin-1 calcium-activated chloride channel (CaCC) contributes to a range of vital functions, such as the control of vascular tone and epithelial ion transport. The channel is a founding member of a family of 10 proteins (TMEM16x) with varied functions; some members (i.e., TMEM16A and TMEM16B) serve as CaCCs, while others are lipid scramblases, combine channel and scramblase function, or perform additional cellular roles. TMEM16x proteins are typically activated by agonist-induced Ca2+ release evoked by Gq-protein-coupled receptor (GqPCR) activation; thus, TMEM16x proteins link Ca2+-signalling with cell electrical activity and/or lipid transport. Recent studies demonstrate that a range of other cellular factors—including plasmalemmal lipids, pH, hypoxia, ATP and auxiliary proteins—also control the activity of the TMEM16A channel and its paralogues, suggesting that the TMEM16x proteins are effectively polymodal sensors of cellular homeostasis. Here, we review the molecular pathophysiology, structural biology, and mechanisms of regulation of TMEM16x proteins by multiple cellular factors.
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