The Sixth Transmembrane Segment Is a Major Gating Component of the TMEM16A Calcium-Activated Chloride Channel

Peters Christian J.; Gilchrist John M.; Tien Jason; Bethel Neville P.; Qi Lijun; Chen Tingxu; Wang Lynn; Jan Yuh Nung; Grabe Michael; Jan Lily Y.

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The Sixth Transmembrane Segment Is a Major Gating Component of the TMEM16A Calcium-Activated Chloride Channel

机译：第六跨膜段是TMEM16A钙活化氯化物通道的主要浇注组分

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Calcium-activated chloride channels (CaCCs) formed by TMEM16A or TMEM16B are broadly expressed in the nervous system, smooth muscles, exocrine glands, and other tissues. With two calcium-binding sites and a pore within each monomer, the dimeric CaCC exhibits voltage-dependent calcium sensitivity. Channel activity also depends on the identity of permeant anions. To understand how CaCC regulates neuronal signaling and how CaCC is, in turn, modulated by neuronal activity, we examined the molecular basis of CaCC gating. Here, we report that voltage modulation of TMEM16A-CaCC involves voltage-dependent occupancy of calcium- and anion-binding site(s) within the membrane electric field as well as a voltage-dependent conformational change intrinsic to the channel protein. These gating modalities all critically depend on the sixth transmembrane segment.

机译：由TMEM16A或TMEM16B形成的钙激活的氯化物通道（CACCs）在神经系统，平滑肌，外分泌腺和其他组织中广泛地表达。在每种单体内有两个钙结合位点和孔，二聚体CACC表现出电压依赖性钙敏感性。频道活动还取决于渗透阴离子的身份。要了解CACC如何调节神经元信号传导以及CACC如何通过神经元活性调节，我们检查了CACC门控的分子基础。这里，我们报告了TMEM16A-CACC的电压调制涉及膜电场内的钙和阴离子结合位点的电压依赖性，以及通道蛋白的电压依赖性构象变化。这些浇注方式所有人都依赖于第六跨膜段。

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《Neuron》 |2018年第5期|共19页
作者
Peters Christian J.; Gilchrist John M.; Tien Jason; Bethel Neville P.; Qi Lijun; Chen Tingxu; Wang Lynn; Jan Yuh Nung; Grabe Michael; Jan Lily Y.;
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Univ Calif San Francisco Dept Physiol San Francisco CA 94158 USA;

Univ Calif San Francisco Dept Physiol San Francisco CA 94158 USA;

Univ Calif San Francisco Dept Physiol San Francisco CA 94158 USA;

Univ Calif San Francisco Dept Pharmaceut Chem San Francisco CA 94158 USA;

Univ Calif San Francisco Dept Physiol San Francisco CA 94158 USA;

Univ Calif San Francisco Dept Physiol San Francisco CA 94158 USA;

Univ Calif San Francisco Dept Physiol San Francisco CA 94158 USA;

Univ Calif San Francisco Dept Physiol San Francisco CA 94158 USA;

Univ Calif San Francisco Dept Pharmaceut Chem San Francisco CA 94158 USA;

Univ Calif San Francisco Dept Physiol San Francisco CA 94158 USA;

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原文格式 PDF
正文语种 eng
中图分类神经病学;
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1. The Sixth Transmembrane Segment Is a Major Gating Component of the TMEM16A Calcium-Activated Chloride Channel [J] . Peters Christian J., Gilchrist John M., Tien Jason, Neuron . 2018,第5期

机译：第六跨膜段是TMEM16A钙活化氯化物通道的主要浇注组分
2. Substituted 2-Acylaminocycloalkylthiophene-3-carboxylic Acid Arylamides as Inhibitors of the Calcium-Activated Chloride Channel Transmembrane Protein 16A (TMEM16A) [J] . Truong Eric C., Phuan Puay W., Reggi Amanda L., Journal of Medicinal Chemistry . 2017,第11期

机译：取代的2-酰氨环环烷基硫戊烯-3-羧酸芳基胺作为钙激活氯通道跨膜蛋白16a的抑制剂（tmem16a）
3. Gating modes of calcium-activated chloride channels TMEM16A and TMEM16B [J] . Cruz-Rangel Silvia, De Jesus-Perez Jose J., Contreras-Vite Juan A., The Journal of Physiology . 2015,第24期

机译：钙激活的氯离子通道TMEM16A和TMEM16B的门控模式
4. Expression Clone of TMEM16A as a Calcium-Activated Chloride Channels in CHO Cells [C] . Feng Hao, Yiju Hou, Chen Zhao, ICASET 2013 . 2013

机译：TMEM16a的表达克隆作为CHO细胞中的钙激活氯化物通道
5. Regulatory and Gating Mechanisms of TMEM16A Chloride Channel [D] . Le, Son Cong. 2021

机译：TMEM16A氯通道的调节和门控机制
6. The sixth transmembrane segment is a major gating component of the TMEM16A calcium-activated chloride channel [O] . Christian J. Peters, John M. Gilchrist, Jason Tien, -1

机译：第六个跨膜片段是TMEM16A钙激活的氯离子通道的主要门控部分
7. The Sixth Transmembrane Segment Is a Major Gating Component of the TMEM16A Calcium-Activated Chloride Channel [O] . Christian J. Peters, John M. Gilchrist, Jason Tien, 2018

机译：第六跨膜段是TMEM16A钙活化氯化物通道的主要浇注组分

The Sixth Transmembrane Segment Is a Major Gating Component of the TMEM16A Calcium-Activated Chloride Channel

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