Studies on expression and function of the TMEM16A calcium-activated chloride channel.
Calcium-activated chloride channels (CaCC) with similar hallmark features are present in many cell types and mediate important physiological functions including epithelial secretion, sensory signal transduction, and smooth muscle contraction. Having identified TMEM16A of the transmembrane proteins with unknown function (TMEM) 16 family as a CaCC subunit, we have developed antibodies specific for mouse TMEM16A, as evidenced by the absence of immunoreactivity in TMEM16A knockout mice. Here, we show that TMEM16A is located in the apical membranes of epithelial cells in exocrine glands and trachea. In addition, TMEM16A is expressed in airway smooth muscle cells and the smooth muscle cells of reproductive tracts, the oviduct and ductus epididymis. In the gastrointestinal (GI) tract, TMEM16A is absent from smooth muscle cells, but present in the interstitial cells of Cajal (ICC), the pacemaker cells that control smooth muscle contraction. The physiological importance of TMEM16A is underscored by the diminished rhythmic contraction of gastric smooth muscle from TMEM16A knockout mice. The TMEM16A expression pattern established in this study thus provides a roadmap for the analyses of physiological functions of calcium-activated chloride channels that contain TMEM16A subunits.
Huang
Fen
F
Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.
Rock
Jason R
JR
Harfe
Brian D
BD
Cheng
Tong
T
Huang
Xiaozhu
X
Jan
Yuh Nung
YN
Jan
Lily Yeh
LY
D000818:Animals; D000075369:Anoctamin-1; D000911:Antibodies, Monoclonal; D018118:Chloride Channels / Q000032:analysis*; D005088:Exocrine Glands / Q000737:chemistry / Q000166:cytology; D041981:Gastrointestinal Tract / Q000737:chemistry / Q000166:cytology; D007150:Immunohistochemistry; D051379:Mice; D014018:Tissue Distribution; D014132:Trachea / Q000737:chemistry / Q000166:cytology; D014566:Urogenital System / Q000737:chemistry / Q000166:cytology
C531181:ANO1 protein, mouse; D000075369:Anoctamin-1; D000911:Antibodies, Monoclonal; D018118:Chloride Channels