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dc.contributor.authorSaha, Tultul
dc.contributor.authorAoun, Joydeep
dc.contributor.authorHayashi, Mikio
dc.contributor.authorAli, Sheikh Irshad
dc.contributor.authorSarkar, Paramita
dc.contributor.authorBag, Prasanta Kumar
dc.contributor.authorLeblanc, Normand
dc.contributor.authorAmeen, Nadia
dc.contributor.authorWoodward, Owen M.
dc.contributor.authorHoque, Kazi Mirajul
dc.date.accessioned2021-02-11T20:18:01Z
dc.date.available2021-02-11T20:18:01Z
dc.date.issued2021-01-22
dc.identifier.urihttp://hdl.handle.net/10713/14677
dc.description.abstractTMEM16A (Transmembrane protein 16A or Anoctamin1) is a calcium-activated chloride channel. (CaCC),that exerts critical roles in epithelial secretion. However, its localization, function, and regulation in intestinal chloride (Cl−) secretion remain obscure. Here, we show that TMEM16A protein abundance correlates with Cl− secretion in different regions of native intestine activated by the Ca2+-elevating muscarinic agonist carbachol (CCH). Basal, as well as both cAMP- and CCH-stimulated Isc, was largely reduced in Ano1 ± mouse intestine. We found CCH was not able to increase Isc in the presence of apical to serosal Cl− gradient, strongly supporting TMEM16A as primarily a luminal Cl− channel. Immunostaining demonstrated apical localization of TMEM16A where it colocalized with NHERF1 in mouse colonic tissue. Cellular depletion of NHERF1 in human colonic T84 cells caused a significant reduction of both cAMP- and CCH-stimulated Isc. Immunoprecipitation experiments revealed that NHERF1 forms a complex with TMEM16A through a PDZ-based interaction. We conclude that TMEM16A is a luminal Cl− channel in the intestine that functionally interacts with CFTR via PDZ-based interaction of NHERF1 for efficient and specific cholinergic stimulation of intestinal Cl− secretion.en_US
dc.description.sponsorshipNational Institutes of Healthen_US
dc.description.urihttps://doi.org/10.1016/j.bbrep.2021.100912en_US
dc.language.isoenen_US
dc.publisherElsevier B.V.en_US
dc.relation.ispartofBiochemistry and Biophysics Reportsen_US
dc.subjectAno1en_US
dc.subjectCystic fibrosisen_US
dc.subjectIntestineen_US
dc.subjectNHERF1en_US
dc.subjectSecretionen_US
dc.subjectTMEM16Aen_US
dc.titleIntestinal TMEM16A control luminal chloride secretion in a NHERF1 dependent manneren_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.bbrep.2021.100912
dc.source.volume25


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