TMEM16A confers receptor-activated calcium-dependent chloride conductance

被引:1055
作者
Yang, Young Duk [1 ]
Cho, Hawon [1 ]
Koo, Jae Yeon [1 ]
Tak, Min Ho [1 ]
Cho, Yeongyo [1 ]
Shim, Won-Sik [1 ]
Park, Seung Pyo [1 ]
Lee, Jesun [1 ]
Lee, Byeongjun [1 ]
Kim, Byung-Moon [1 ]
Raouf, Ramin [2 ]
Shin, Young Ki [1 ]
Oh, Uhtaek [1 ]
机构
[1] Seoul Natl Univ, Sensory Res Ctr, CRI, Coll Pharm, Seoul 151742, South Korea
[2] UCL, Mol Nocicept Grp, London WC1E 6BT, England
基金
英国惠康基金;
关键词
D O I
10.1038/nature07313
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Calcium (Ca2+)-activated chloride channels are fundamental mediators in numerous physiological processes including transepithelial secretion, cardiac and neuronal excitation, sensory transduction, smooth muscle contraction and fertilization. Despite their physiological importance, their molecular identity has remained largely unknown. Here we show that transmembrane protein 16A(TMEM16A, which we also call anoctamin 1 (ANO1)) is a bona fide Ca2+-activated chloride channel that is activated by intracellular Ca2+ and Ca2+- mobilizing stimuli. With eight putative transmembrane domains and no apparent similarity to previously characterized channels, ANO1 defines a new family of ionic channels. The biophysical properties as well as the pharmacological profile of ANO1 are in full agreement with native Ca2+- activated chloride currents. ANO1 is expressed in various secretory epithelia, the retina and sensory neurons. Furthermore, knockdown of mouse Ano1 markedly reduced native Ca2+-activated chloride currents as well as saliva production in mice. We conclude that ANO1 is a candidate Ca2+-activated chloride channel that mediates receptor- activated chloride currents in diverse physiological processes.
引用
收藏
页码:1210 / U36
页数:7
相关论文
共 42 条
[1]   CALCIUM AND CAMP ACTIVATE DIFFERENT CHLORIDE CHANNELS IN THE APICAL MEMBRANE OF NORMAL AND CYSTIC-FIBROSIS EPITHELIA [J].
ANDERSON, MP ;
WELSH, MJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (14) :6003-6007
[2]   A novel chloride conductance activated by extracellular ATP in mouse parotid acinar cells [J].
Arreola, J ;
Melvin, JE .
JOURNAL OF PHYSIOLOGY-LONDON, 2003, 547 (01) :197-208
[3]   Secretion and cell volume regulation by salivary acinar cells from mice lacking expression of the Clcn3 Cl- channel gene [J].
Arreola, J ;
Begenisich, T ;
Nehrke, K ;
Nguyen, HV ;
Park, K ;
Richardson, L ;
Yang, BL ;
Schutte, BC ;
Lamb, FS ;
Melvin, JE .
JOURNAL OF PHYSIOLOGY-LONDON, 2002, 545 (01) :207-216
[4]   Activation of calcium-dependent chloride channels in rat parotid acinar cells [J].
Arreola, J ;
Melvin, JE ;
Begenisich, T .
JOURNAL OF GENERAL PHYSIOLOGY, 1996, 108 (01) :35-47
[5]   CHLORIDE SECRETORY RESPONSE OF CYSTIC-FIBROSIS HUMAN AIRWAY EPITHELIA - PRESERVATION OF CALCIUM BUT NOT PROTEIN-KINASE C-DEPENDENT AND A-DEPENDENT MECHANISMS [J].
BOUCHER, RC ;
CHENG, EHC ;
PARADISO, AM ;
STUTTS, MJ ;
KNOWLES, MR ;
EARP, HS .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 84 (05) :1424-1431
[6]   Head and neck squamous cell carcinoma transcriptome analysis by comprehensive validated differential display [J].
Carles, A ;
Millon, R ;
Cromer, A ;
Ganguli, G ;
Lemaire, F ;
Young, J ;
Wasylyk, C ;
Muller, D ;
Schultz, I ;
Rabouel, Y ;
Dembélé, D ;
Zhao, C ;
Marchal, P ;
Ducray, C ;
Bracco, L ;
Abecassis, J ;
Poch, O ;
Wasylyk, B .
ONCOGENE, 2006, 25 (12) :1821-1831
[7]   Cloning of an epithelial chloride channel from bovine trachea [J].
Cunningham, SA ;
Awayda, MS ;
Bubien, JK ;
Ismailov, II ;
Arrate, MP ;
Berdiev, BK ;
Benos, DJ ;
Fuller, CM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (52) :31016-31026
[8]  
Eggermont Jan, 2004, Proc Am Thorac Soc, V1, P22, DOI 10.1513/pats.2306010
[9]   Tumor suppression by a proapoptotic calcium-activated chloride channel in mammary epithelium [J].
Elble, RC ;
Pauli, BU .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (44) :40510-40517
[10]   A novel monoclonal antibody against DOG1 is a sensitive and specific marker for gastrointestinal stromal tumors [J].
Espinosa, Inigo ;
Lee, Cheng-Han ;
Kim, Mi Kyung ;
Rouse, Bich-Tien ;
Subramanian, Subbaya ;
Montgomery, Kelli ;
Varma, Sushama ;
Corless, Christopher L. ;
Heinrich, Michael C. ;
Smith, Kevin S. ;
Wang, Zhong ;
Rubin, Brian ;
Nielsen, Torsten O. ;
Seitz, Robert S. ;
Ross, Douglas T. ;
West, Robert B. ;
Cleary, Michael L. ;
van de Rijn, Matt .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2008, 32 (02) :210-218