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

Autor:	Peters CJ; Departments of Physiology, Biophysics and Biochemistry, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: christian.peters@ucsf.edu., Gilchrist JM; Departments of Physiology, Biophysics and Biochemistry, University of California, San Francisco, San Francisco, CA 94158, USA., Tien J; Departments of Physiology, Biophysics and Biochemistry, University of California, San Francisco, San Francisco, CA 94158, USA., Bethel NP; Department of Pharmaceutical Chemistry and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA., Qi L; Departments of Physiology, Biophysics and Biochemistry, University of California, San Francisco, San Francisco, CA 94158, USA., Chen T; Departments of Physiology, Biophysics and Biochemistry, University of California, San Francisco, San Francisco, CA 94158, USA., Wang L; Departments of Physiology, Biophysics and Biochemistry, University of California, San Francisco, San Francisco, CA 94158, USA., Jan YN; Departments of Physiology, Biophysics and Biochemistry, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA., Grabe M; Department of Pharmaceutical Chemistry and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA., Jan LY; Departments of Physiology, Biophysics and Biochemistry, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: lily.jan@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2018 Mar 07; Vol. 97 (5), pp. 1063-1077.e4. Date of Electronic Publication: 2018 Feb 22.
DOI:	10.1016/j.neuron.2018.01.048
Abstrakt:	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. (Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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