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

被引：70

作者：

Peters, Christian J. ^{[1
,2
,3
]}

Gilchrist, John M. ^{[1
,2
,3
]}

Tien, Jason ^{[1
,2
,3
]}

Bethel, Neville P. ^{[4
,5
]}

Qi, Lijun ^{[1
,2
,3
]}

Chen, Tingxu ^{[1
,2
,3
]}

Wang, Lynn ^{[1
,2
,3
]}

Jan, Yuh Nung ^{[1
,2
,3
,6
]}

Grabe, Michael ^{[4
,5
]}

Jan, Lily Y. ^{[1
,2
,3
,6
]}

机构：

[1] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA

[2] Univ Calif San Francisco, Dept Biophys, San Francisco, CA 94158 USA

[3] Univ Calif San Francisco, Dept Biochem, San Francisco, CA 94158 USA

[4] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA

[5] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA

[6] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA

来源：

NEURON | 2018年 / 97卷 / 05期

关键词：

SHAKER POTASSIUM CHANNEL; ADDITIVE FORCE-FIELD; SMOOTH-MUSCLE; INDEPENDENT ACTIVATION; CRYO-EM; PROTEIN; EXPRESSION; BLOCKER; SCRAMBLASE; MECHANISM;

D O I：

10.1016/j.neuron.2018.01.048

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：1063 / +

页数：19

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