دورية أكاديمية
The Sixth Transmembrane Segment Is a Major Gating Component of the TMEM16A Calcium-Activated Chloride Channel.
| العنوان: | The Sixth Transmembrane Segment Is a Major Gating Component of the TMEM16A Calcium-Activated Chloride Channel. |
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| المؤلفون: | 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. |
| المصدر: | Neuron [Neuron] 2018 Mar 07; Vol. 97 (5), pp. 1063-1077.e4. Date of Electronic Publication: 2018 Feb 22. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 8809320 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4199 (Electronic) Linking ISSN: 08966273 NLM ISO Abbreviation: Neuron Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Cambridge, Mass. : Cell Press, c1988- |
| مواضيع طبية MeSH: | Anoctamin-1/*chemistry , Anoctamin-1/*metabolism , Chloride Channels/*chemistry , Chloride Channels/*metabolism , Ion Channel Gating/*physiology, Amino Acid Sequence ; Animals ; Anoctamin-1/genetics ; Chloride Channels/genetics ; HEK293 Cells ; Humans ; Mice ; Protein Binding/physiology ; Protein Structure, Secondary |
| مستخلص: | 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.) |
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| معلومات مُعتمدة: | R01 NS069229 United States NS NINDS NIH HHS; T32 EB009383 United States EB NIBIB NIH HHS; R01 GM089740 United States GM NIGMS NIH HHS; R01 GM117593 United States GM NIGMS NIH HHS; K99 DA041500 United States DA NIDA NIH HHS |
| المشرفين على المادة: | 0 (ANO1 protein, mouse) 0 (Anoctamin-1) 0 (Chloride Channels) |
| تواريخ الأحداث: | Date Created: 20180227 Date Completed: 20190715 Latest Revision: 20210109 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC5860880 |
| DOI: | 10.1016/j.neuron.2018.01.048 |
| PMID: | 29478917 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1097-4199 |
|---|---|
| DOI: | 10.1016/j.neuron.2018.01.048 |