{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T12:38:22Z","timestamp":1782995902201,"version":"3.54.5"},"reference-count":69,"publisher":"The Company of Biologists","issue":"24","license":[{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"vor","delay-in-days":58,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1R01DK123463-01"],"award-info":[{"award-number":["1R01DK123463-01"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001463","name":"American Society of Nephrology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001463","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Approximately 15% of autosomal dominant polycystic kidney disease (ADPKD) is caused by variants in PKD2. PKD2 encodes polycystin-2, which forms an ion channel in primary cilia and endoplasmic reticulum (ER) membranes of renal collecting duct cells. Elevated internal Ca2+ modulates polycystin-2 voltage-dependent gating and subsequent desensitization \u2013 two biophysical regulatory mechanisms that control its function at physiological membrane potentials. Here, we refute the hypothesis that Ca2+ occupancy of the polycystin-2 intracellular EF hand is responsible for these forms of channel regulation, and, if disrupted, results in ADPKD. We identify and introduce mutations that attenuate Ca2+-EF hand affinity but find channel function is unaltered in the primary cilia and ER membranes. We generated two new mouse strains that harbor distinct mutations that abolish Ca2+-EF hand association but do not result in a PKD phenotype. Our findings suggest that additional Ca2+-binding sites within polycystin-2 or Ca2+-dependent modifiers are responsible for regulating channel activity.<\/jats:p>","DOI":"10.1242\/jcs.255562","type":"journal-article","created":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T15:07:00Z","timestamp":1605539220000},"source":"Crossref","is-referenced-by-count":17,"title":["Disrupting polycystin-2 EF hand Ca2+ affinity does not alter channel function or contribute to polycystic kidney disease"],"prefix":"10.1242","volume":"133","author":[{"given":"Thuy N.","family":"Vien","sequence":"first","affiliation":[{"name":"Feinberg School of Medicine, Northwestern University 1 Department of Pharmacology , , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo C. T.","family":"Ng","sequence":"additional","affiliation":[{"name":"Feinberg School of Medicine, Northwestern University 1 Department of Pharmacology , , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Mayo Clinic 2 Division of Nephrology and Hypertension , , Rochester, MN 55905 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Dong","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine 3 Departments of Internal Medicine and Genetics , , New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteus","family":"Krappitz","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine 3 Departments of Internal Medicine and Genetics , , New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir G.","family":"Gainullin","sequence":"additional","affiliation":[{"name":"Mayo Clinic 2 Division of Nephrology and Hypertension , , Rochester, MN 55905 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sorin","family":"Fedeles","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine 3 Departments of Internal Medicine and Genetics , , New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Harris","sequence":"additional","affiliation":[{"name":"Mayo Clinic 2 Division of Nephrology and Hypertension , , Rochester, MN 55905 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Somlo","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine 3 Departments of Internal Medicine and Genetics , , New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8776-983X","authenticated-orcid":false,"given":"Paul G.","family":"DeCaen","sequence":"additional","affiliation":[{"name":"Feinberg School of Medicine, Northwestern University 1 Department of Pharmacology , , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,12,24]]},"reference":[{"key":"2024061319125620900_JCS255562C1","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1002\/pro.2513","article-title":"A high-resolution structure of the EF-hand domain of human polycystin-2","volume":"23","author":"Allen","year":"2014","journal-title":"Protein Sci."},{"key":"2024061319125620900_JCS255562C2","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1085\/jgp.201311153","article-title":"Calmodulin regulation (calmodulation) of voltage-gated calcium channels","volume":"143","author":"Ben-Johny","year":"2014","journal-title":"J. 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