{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:37:42Z","timestamp":1761709062051},"reference-count":41,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2003,12]]},"abstract":"<jats:p>The precise steps leading from mutation of the polycystic kidney disease ( PKD1) gene to the autosomal dominant polycystic kidney disease (ADPKD) phenotype remain to be established. Fluid accumulation is a requirement for cyst expansion in ADPKD, suggesting that abnormal fluid secretion into the cyst lumen might play a role in disease. In this study, we sought to establish a link between polycystin-1 (the PKD1 gene product) and ATP-stimulated Cl<jats:sup>\u2013<\/jats:sup>secretion in renal tubule cells. To do this, we performed a whole cell patch-clamp analysis of the effects of expression of the isolated cytoplasmic COOH-terminus of polycystin-1 in stably transfected mouse cortical collecting duct cells. The truncated polycystin-1 fusion protein prolonged the duration of ATP-stimulated Cl<jats:sup>\u2013<\/jats:sup>conductance and intracellular Ca<jats:sup>2+<\/jats:sup>responses. Both effects were dependent on extracellular Ca<jats:sup>2+<\/jats:sup>. It was determined that expression of the truncated polycystin-1 fusion protein introduced, or activated, an ATP-induced Ca<jats:sup>2+<\/jats:sup>entry pathway that was undetectable in transfection control cell lines. Our findings are concordant with increasing evidence for a role of polycystin-1 in cell Ca<jats:sup>2+<\/jats:sup>homeostasis and indicate that dysregulated Ca<jats:sup>2+<\/jats:sup>entry might promote Cl<jats:sup>\u2013<\/jats:sup>secretion and cyst expansion in ADPKD.<\/jats:p>","DOI":"10.1152\/ajprenal.00171.2003","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:39:50Z","timestamp":1425415190000},"page":"F1168-F1178","source":"Crossref","is-referenced-by-count":25,"title":["The isolated polycystin-1 cytoplasmic COOH terminus prolongs ATP-stimulated Cl<sup>\u2013<\/sup>conductance through increased Ca<sup>2+<\/sup>entry"],"prefix":"10.1152","volume":"285","author":[{"given":"Scott S.","family":"Wildman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly M.","family":"Hooper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clare M.","family":"Turner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James S. K.","family":"Sham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward G.","family":"Lakatta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian F.","family":"King","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Unwin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Sutters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"REF1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)03011-5"},{"key":"REF2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.11.6013"},{"key":"REF3","unstructured":"Bailey MA, Imbert-Teboul M, Turner C, Srai SK, Burnstock G, and Unwin RJ.Evidence for basolateral P2Y6 receptors along the rat proximal tubule: functional and molecular characterization.J Am Soc Nephrol12: 1640\u20131647, 2001."},{"key":"REF4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.62.1.535"},{"key":"REF5","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.1.F92"},{"key":"REF6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.t01-1-00325.x"},{"key":"REF7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1990.259.1.C19"},{"key":"REF8","doi-asserted-by":"crossref","unstructured":"Carew MA, Yang X, Schultz C, and Shears SB.Myo-inositol 3,4,5,6-tetrakisphosphate inhibits an apical calcium-activated chloride conductance in polarized monolayers of a cystic fibrosis cell line.J Biol Chem275: 26906\u201326913, 2000.","DOI":"10.1074\/jbc.M002316200"},{"key":"REF9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00077.x"},{"key":"REF10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.22.10449"},{"key":"REF11","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90137-6"},{"key":"REF12","doi-asserted-by":"publisher","DOI":"10.1007\/PL00008086"},{"key":"REF13","doi-asserted-by":"publisher","DOI":"10.1053\/ajkd.2002.33379"},{"key":"REF14","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.48.32096"},{"key":"REF15","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00384.2001"},{"key":"REF16","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050173"},{"key":"REF17","doi-asserted-by":"crossref","unstructured":"Hanaoka Kand Guggino W.cAMP regulates cell proliferation and cyst formation in autosomal polycystic kidney disease cells.J Am Soc Nephrol11: 1179\u20131187, 2000.","DOI":"10.1681\/ASN.V1171179"},{"key":"REF18","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(92)90687-K"},{"key":"REF19","doi-asserted-by":"publisher","DOI":"10.1042\/cs1040217"},{"key":"REF20","doi-asserted-by":"crossref","unstructured":"International Polycystic Kidney Disease Consortium.Polycystic kidney disease: the complete structure of the PKD1 gene, and its protein.Cell81: 89\u201398, 1995.","DOI":"10.1016\/0092-8674(95)90339-9"},{"key":"REF21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.11.6371"},{"key":"REF22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.8.4947"},{"key":"REF23","unstructured":"King BFand Burnstock G.Understanding G protein-coupled receptors and their role in the CNS. In:Purinergic Receptors, edited by Davies CH. Philadelphia, PA: Oxford Univ. Press, 2002, chapt. 21, p. 422\u2013439."},{"key":"REF24","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.115.1.59"},{"key":"REF25","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.21.2385"},{"key":"REF26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.11.5113"},{"key":"REF27","doi-asserted-by":"publisher","DOI":"10.1038\/ng1076"},{"key":"REF28","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0212867"},{"key":"REF29","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9514"},{"key":"REF30","doi-asserted-by":"crossref","unstructured":"Putney JWJr, Broad LM, Braun F-J, Lievremont J-P, and Bird GSJ.Mechanisms of capacitative calcium entry.J Cell Sci114: 2223\u20132229, 2001.","DOI":"10.1242\/jcs.114.12.2223"},{"key":"REF31","doi-asserted-by":"crossref","unstructured":"Rubera I, Tauc M, Bidet M, Verheecke-Mauze C, De Renzis G, Poujeol C, Cuiller B, and Poujeol P.Extracellular ATP increases [Ca2+]iin distal tubule cells. II. Activation of a Ca2+-dependent Cl\u2013conductance.Am J Physiol Renal Physiol279: F102\u2013F111, 2000.","DOI":"10.1152\/ajprenal.2000.279.1.F102"},{"key":"REF32","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.0337.2000"},{"key":"REF33","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1991.148"},{"key":"REF34","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(01)00875-5"},{"key":"REF35","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1998.78.4.1165"},{"key":"REF36","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.060002484.x"},{"key":"REF37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.7.3934"},{"key":"REF38","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006252200"},{"key":"REF39","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(98)90079-3"},{"key":"REF40","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80302-5"},{"key":"REF41","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00991.x"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00171.2003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,1]],"date-time":"2022-05-01T09:39:05Z","timestamp":1651397945000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00171.2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,12]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2003,12]]}},"alternative-id":["10.1152\/ajprenal.00171.2003"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00171.2003","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,12]]}}}