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http://purl.uniprot.org/citations/32422433http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/32422433http://www.w3.org/2000/01/rdf-schema#comment"Chloride fluxes through the calcium-gated chloride channel Anoctamin-1 (TMEM16A) control blood pressure, secretion of saliva, mucin, insulin, and melatonin, gastrointestinal motility, sperm capacitation and motility, and pain sensation. Calcium activates a myriad of regulatory proteins but how these proteins affect TMEM16A activity is unresolved. Here we show by co-immunoprecipitation that increasing intracellular calcium with ionomycin or by activating sphingosine-1-phosphate receptors, induces coupling of calcium/calmodulin-dependent phosphatase calcineurin and prolyl isomerase FK506-binding protein 12 (FKBP12) to TMEM16A in HEK-293 cells. Application of drugs that target either calcineurin (cyclosporine A) or FKBP12 (tacrolimus known as FK506 and sirolimus known as rapamycin) caused a decrease in TMEM16A activity. In addition, FK506 and BAPTA-AM prevented co-immunoprecipitation between FKBP12 and TMEM16A. FK506 rendered the channel insensitive to cyclosporine A without altering its apparent calcium sensitivity whereas zero intracellular calcium blocked the effect of FK506. Rapamycin decreased TMEM16A activity in cells pre-treated with cyclosporine A or FK506. These results suggest the formation of a TMEM16A-FKBP12-calcineurin complex that regulates channel function. We conclude that upon a cytosolic calcium increase the TMEM16A-FKPB12-calcineurin trimers are assembled. Such hetero-oligomerization enhances TMEM16A channel activity but is not mandatory for activation by calcium."xsd:string
http://purl.uniprot.org/citations/32422433http://purl.org/dc/terms/identifier"doi:10.1016/j.ceca.2020.102211"xsd:string
http://purl.uniprot.org/citations/32422433http://purl.uniprot.org/core/author"Guzman-Hernandez M.L."xsd:string
http://purl.uniprot.org/citations/32422433http://purl.uniprot.org/core/author"Arreola J."xsd:string
http://purl.uniprot.org/citations/32422433http://purl.uniprot.org/core/author"Perez-Cornejo P."xsd:string
http://purl.uniprot.org/citations/32422433http://purl.uniprot.org/core/author"Cruz-Rangel S."xsd:string
http://purl.uniprot.org/citations/32422433http://purl.uniprot.org/core/author"Sanchez-Solano A."xsd:string
http://purl.uniprot.org/citations/32422433http://purl.uniprot.org/core/author"Segura-Covarrubias G."xsd:string
http://purl.uniprot.org/citations/32422433http://purl.uniprot.org/core/author"Arechiga-Figueroa I."xsd:string
http://purl.uniprot.org/citations/32422433http://purl.uniprot.org/core/author"Corral N."xsd:string
http://purl.uniprot.org/citations/32422433http://purl.uniprot.org/core/date"2020"xsd:gYear
http://purl.uniprot.org/citations/32422433http://purl.uniprot.org/core/name"Cell Calcium"xsd:string
http://purl.uniprot.org/citations/32422433http://purl.uniprot.org/core/pages"102211"xsd:string
http://purl.uniprot.org/citations/32422433http://purl.uniprot.org/core/title"Regulation of the Ca2+-activated chloride channel Anoctamin-1 (TMEM16A) by Ca2+-induced interaction with FKBP12 and calcineurin."xsd:string
http://purl.uniprot.org/citations/32422433http://purl.uniprot.org/core/volume"89"xsd:string
http://purl.uniprot.org/citations/32422433http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/32422433
http://purl.uniprot.org/citations/32422433http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/32422433
http://purl.uniprot.org/uniprot/#_A0A0G2QSF1-mappedCitation-32422433http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32422433
http://purl.uniprot.org/uniprot/#_A0A087WTS4-mappedCitation-32422433http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32422433
http://purl.uniprot.org/uniprot/#_Q0VDC5-mappedCitation-32422433http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32422433
http://purl.uniprot.org/uniprot/#_Q0VDC6-mappedCitation-32422433http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32422433
http://purl.uniprot.org/uniprot/#_Q1JUQ3-mappedCitation-32422433http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32422433
http://purl.uniprot.org/uniprot/#_Q1JUQ5-mappedCitation-32422433http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32422433
http://purl.uniprot.org/uniprot/#_A0A0S2Z4B5-mappedCitation-32422433http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32422433