Insights into the function and regulation of the calcium-activated chloride channel TMEM16A

被引:0
作者
Arreola, Jorge [1 ]
Elena Lopez-Romero, Ana [1 ]
Huerta, Miriam [1 ]
Luisa Guzman- Hernandez, Maria [2 ]
Perez-Cornejo, Patricia [3 ]
机构
[1] Univ Autonoma San Luis Potosi, Phys Inst, Ave Parque Chapultepec 1570, San Luis Potosi 78295, Slp, Mexico
[2] Univ Autonoma San Luis Potosi, Sch Med, Dept Physiol & Biophys, Catedrat CONAHCYT, Ave V Carranza 2905, San Luis Potosi 78210, Slp, Mexico
[3] Univ Autonoma San Luis Potosi, Sch Med, Dept Physiol & Biophys, Ave V Carranza 2905, San Luis Potosi 78210, Slp, Mexico
关键词
TMEM16A; Chloride channel; Calcium; Function; Regulation; Structure; CA2+-ACTIVATED CL-CHANNEL; INTERSTITIAL-CELLS; ANOCTAMIN; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; INDEPENDENT ACTIVATION; ENDOTHELIAL-CELLS; ION CHANNELS; ANO1; EXPRESSION; CONDUCTANCE;
D O I
10.1016/j.ceca.2024.102891
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The TMEM16A channel, a member of the TMEM16 protein family comprising chloride (Cl-) channels and lipid scramblases, is activated by the free intracellular Ca2+ increments produced by inositol 1,4,5-trisphosphate (IP3)induced Ca2+ release after GqPCRs or Ca2+ entry through cationic channels. It is a ubiquitous transmembrane protein that participates in multiple physiological functions essential to mammals' lives. TMEM16A structure contains two identical 10-segment monomers joined at their transmembrane segment 10. Each monomer harbours one independent hourglass-shaped pore gated by Ca2+ ligation to an orthosteric site adjacent to the pore and controlled by two gates. The orthosteric site is created by assembling negatively charged glutamate side chains near the pore's cytosolic end. When empty, this site generates an electrostatic barrier that controls channel rectification. In addition, an isoleucine-triad forms a hydrophobic gate at the boundary of the cytosolic vestibule and the inner side of the neck. When the cytosolic Ca2+ rises, one or two Ca2+ ions bind to the orthosteric site in a voltage (V)-dependent manner, thus neutralising the electrostatic barrier and triggering an allosteric gating mechanism propagating via transmembrane segment 6 to the hydrophobic gate. These coordinated events lead to pore opening, allowing the Cl- flux to ensure the physiological response. The Ca2+-dependent function of TMEM16A is highly regulated. Anions with higher permeability than Cl- facilitate V dependence by increasing the Ca2+ sensitivity, intracellular protons can replace Ca2+ and induce channel opening, and phosphatidylinositol 4,5-bisphosphate bound to four cytosolic sites likely maintains Ca2+ sensitivity. Additional regulation is afforded by cytosolic proteins, most likely by phosphorylation and protein-protein interaction mechanisms.
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页数:15
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共 207 条
  • [41] Cryo-EM structures of the TMEM16A calcium-activated chloride channel
    Dang, Shangyu
    Feng, Shengjie
    Tien, Jason
    Peters, Christian J.
    Bulkley, David
    Lolicato, Marco
    Zhao, Jianhua
    Zuberbuhler, Kathrin
    Ye, Wenlei
    Qi, Lijun
    Chen, Tingxu
    Craik, Charles S.
    Jan, Yuh Nung
    Minor, Daniel L., Jr.
    Cheng, Yifan
    Jan, Lily Yeh
    [J]. NATURE, 2017, 552 (7685) : 426 - +
  • [42] Potent vasorelaxant activity of the TMEM16A inhibitor T16Ainh-A01
    Davis, Alison J.
    Shi, Jian
    Pritchard, Harry A. T.
    Chadha, Preet S.
    Leblanc, Normand
    Vasilikostas, Georgios
    Yao, Zhen
    Verkman, A. S.
    Albert, Anthony P.
    Greenwood, Iain A.
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 2013, 168 (03) : 773 - 784
  • [43] Ca2+-activated Cl- channel TMEM16A/ANO1 identified in zebrafish skeletal muscle is crucial for action potential acceleration
    Dayal, Anamika
    Ng, Shu Fun J.
    Grabner, Manfred
    [J]. NATURE COMMUNICATIONS, 2019, 10 (1)
  • [44] Gating and anion selectivity are reciprocally regulated in TMEM16A (ANO1)
    De Jesus-Perez, Jose J.
    Lopez-Romero, Ana E.
    Posadas, Odalys
    Segura-Covarrubias, Guadalupe
    Arechiga-Figueroa, Ivan
    Gutierrez-Medina, Braulio
    Perez-Cornejo, Patricia
    Arreola, Jorge
    [J]. JOURNAL OF GENERAL PHYSIOLOGY, 2022, 154 (08)
  • [45] Electro-steric opening of the clc-2 chloride channel gate
    De Jesus-Perez, Jose J.
    Arlette Mendez-Maldonado, G.
    Lopez-Romero, Ana E.
    Esparza-Jasso, David
    Gonzalez-Hernandez, Irma L.
    De la Rosa, Victor
    Gastelum-Garibaldi, Roberto
    Sanchez-Rodriguez, Jorge E.
    Arreola, Jorge
    [J]. SCIENTIFIC REPORTS, 2021, 11 (01)
  • [46] Phosphatidylinositol 4,5-bisphosphate, cholesterol, and fatty acids modulate the calcium-activated chloride channel TMEM16A (ANO1)
    De Jesus-Perez, Jose J.
    Cruz-Rangel, Silvia
    Espino-Saldana, Angeles E.
    Martinez-Torres, Ataulfo
    Qu, Zhiqiang
    Criss Hartzell, H.
    Corral-Fernandez, Nancy E.
    Perez-Cornejo, Patricia
    Arreola, Jorge
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2018, 1863 (03): : 299 - 312
  • [47] Gating the glutamate gate of CLC-2 chloride channel by pore occupancy
    De Jesus-Perez, Jose J.
    Castro-Chong, Alejandra
    Shieh, Ru-Chi
    Hernandez-Carballo, Carmen Y.
    De Santiago-Castillo, Jose A.
    Arreola, Jorge
    [J]. JOURNAL OF GENERAL PHYSIOLOGY, 2016, 147 (01) : 25 - 37
  • [48] Anoctamin-1 Cl- channels in nociception: activation by an N-aroylaminothiazole and capsaicin and inhibition by T16A[inh]-A01
    Deba, Farah
    Bessac, Bret F.
    [J]. MOLECULAR PAIN, 2015, 11
  • [49] TRPV4 heats up ANO1-dependent exocrine gland fluid secretion
    Derouiche, Sandra
    Takayama, Yasunori
    Murakami, Masataka
    Tominaga, Makoto
    [J]. FASEB JOURNAL, 2018, 32 (04) : 1841 - 1854
  • [50] Quantitative properties and receptor reserve of the IP3 and calcium branch of Gq-coupled receptor signaling
    Dickson, Eamonn J.
    Falkenburger, Bjoern H.
    Hille, Bertil
    [J]. JOURNAL OF GENERAL PHYSIOLOGY, 2013, 141 (05) : 521 - 535