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The Ca 2+-activated chloride channel ANO1/TMEM16A: An emerging therapeutic target for epithelium-originated diseases?
review-article
09 December 2020
Ca2+-activated Cl– channels (CaCCs),
ANO1,
TMEM16A,
CaCCinh-A01,
T16Ainh-A01,
Drug target,
Cancer,
Cystic fibrosis,
Ang II, angiotensin II,
ANO1, anoctamin-1,
ASM, airway smooth muscle,
BBB, blood–brain barrier,
CaCCs, Ca2+ activated chloride channels,
CAMK, Ca2+/calmodulin-dependent protein kinase,
CF, cystic fibrosis,
CFTR, cystic fibrosis transmembrane conductance regulator,
DRG, dorsal root ganglion,
EGFR, epidermal growth factor receptor,
ENaC, epithelial sodium channels,
ER, endoplasmic reticulum,
ESCC, esophageal squamous cell carcinoma,
FRT, fisher rat thyroid,
GI, gastrointestinal,
GIST, gastrointestinal stromal tumor,
GPCR, G-protein coupled receptor,
HNSCC, head and neck squamous cell carcinoma,
HTS, high-throughput screening,
ICC, interstitial cells of Cajal,
IPAH, idiopathic pulmonary arterial hypertension,
MAPK, mitogen-activated protein kinase,
NF-κB, nuclear factor κB,
PAH, pulmonary arterial hypertension,
PAR2, protease activated receptor 2,
PASMC, pulmonary artery smooth muscle cells,
PIP2, phosphatidylinositol 4,5-bisphosphate,
PKD, polycystic kidney disease,
TGF-β, transforming growth factor-β,
VGCC, voltage gated calcium channel,
VRAC, volume regulated anion channel,
VSMC, vascular smooth muscle cells,
YFP, yellow fluorescent protein
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Abstract
Anoctamin 1 ( ANO1) or TMEM16A gene encodes a member of Ca 2+ activated Cl – channels (CaCCs) that are critical for physiological functions, such as epithelial secretion, smooth muscle contraction and sensory signal transduction. The attraction and interest in ANO1/TMEM16A arise from a decade long investigations that abnormal expression or dysfunction of ANO1 is involved in many pathological phenotypes and diseases, including asthma, neuropathic pain, hypertension and cancer. However, the lack of specific modulators of ANO1 has impeded the efforts to validate ANO1 as a therapeutic target. This review focuses on the recent progress made in understanding of the pathophysiological functions of CaCC ANO1 and the current modulators used as pharmacological tools, hopefully illustrating a broad spectrum of ANO1 channelopathy and a path forward for this target validation.
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Most cited references211
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- Abstract: found
- Article: not found
TMEM16A confers receptor-activated calcium-dependent chloride conductance.
Young Duk Yang, Hawon Cho, Jae Koo … (2008)
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- Abstract: found
- Article: not found
TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity.
Antonella Caputo, Emanuela Caci, Loretta Ferrera … (2008)
Author and article information
ca2+-activated cl– channels (caccs),ano1,tmem16a,caccinh-a01,t16ainh-a01,drug target,cancer,cystic fibrosis,ang ii, angiotensin ii,ano1, anoctamin-1,asm, airway smooth muscle,bbb, blood–brain barrier,caccs, ca2+ activated chloride channels,camk, ca2+/calmodulin-dependent protein kinase,cf, cystic fibrosis,cftr, cystic fibrosis transmembrane conductance regulator,drg, dorsal root ganglion,egfr, epidermal growth factor receptor,enac, epithelial sodium channels,er, endoplasmic reticulum,escc, esophageal squamous cell carcinoma,frt, fisher rat thyroid,gi, gastrointestinal,gist, gastrointestinal stromal tumor,gpcr, g-protein coupled receptor,hnscc, head and neck squamous cell carcinoma,hts, high-throughput screening,icc, interstitial cells of cajal,ipah, idiopathic pulmonary arterial hypertension,mapk, mitogen-activated protein kinase,nf-κb, nuclear factor κb,pah, pulmonary arterial hypertension,par2, protease activated receptor 2,pasmc, pulmonary artery smooth muscle cells,pip2, phosphatidylinositol 4,5-bisphosphate,pkd, polycystic kidney disease,tgf-β, transforming growth factor-β,vgcc, voltage gated calcium channel,vrac, volume regulated anion channel,vsmc, vascular smooth muscle cells,yfp, yellow fluorescent protein
ca2+-activated cl– channels (caccs), ano1, tmem16a, caccinh-a01, t16ainh-a01, drug target, cancer, cystic fibrosis, ang ii, angiotensin ii, ano1, anoctamin-1, asm, airway smooth muscle, bbb, blood–brain barrier, caccs, ca2+ activated chloride channels, camk, ca2+/calmodulin-dependent protein kinase, cf, cystic fibrosis, cftr, cystic fibrosis transmembrane conductance regulator, drg, dorsal root ganglion, egfr, epidermal growth factor receptor, enac, epithelial sodium channels, er, endoplasmic reticulum, escc, esophageal squamous cell carcinoma, frt, fisher rat thyroid, gi, gastrointestinal, gist, gastrointestinal stromal tumor, gpcr, g-protein coupled receptor, hnscc, head and neck squamous cell carcinoma, hts, high-throughput screening, icc, interstitial cells of cajal, ipah, idiopathic pulmonary arterial hypertension, mapk, mitogen-activated protein kinase, nf-κb, nuclear factor κb, pah, pulmonary arterial hypertension, par2, protease activated receptor 2, pasmc, pulmonary artery smooth muscle cells, pip2, phosphatidylinositol 4,5-bisphosphate, pkd, polycystic kidney disease, tgf-β, transforming growth factor-β, vgcc, voltage gated calcium channel, vrac, volume regulated anion channel, vsmc, vascular smooth muscle cells, yfp, yellow fluorescent protein