{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:57:33Z","timestamp":1793692653512,"version":"4.5.1"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,6,28]]},"abstract":"<jats:p>\n                    Polycystic kidney disease (PKD) is a genetic disorder that is characterized by cyst formation in kidney tubules. PKD arises from abnormalities of the primary cilium, a sensory organelle located on the cell surface. Here, we show that the primary cilium of renal epithelial cells contains a protein complex comprising adenylyl cyclase 5\/6 (AC5\/6), A-kinase anchoring protein 150 (AKAP150), and protein kinase A. Loss of primary cilia caused by deletion of\n                    <jats:italic>Kif3a<\/jats:italic>\n                    results in activation of AC5 and increased cAMP levels. Polycystin-2 (PC2), a ciliary calcium channel that is mutated in human PKD, interacts with AC5\/6 through its C terminus. Deletion of PC2 increases cAMP levels, which can be corrected by reexpression of wild-type PC2 but not by a mutant lacking calcium channel activity. Phosphodiesterase 4C (PDE4C), which catabolizes cAMP, is also located in renal primary cilia and interacts with the AKAP150 complex. Expression of PDE4C is regulated by the transcription factor hepatocyte nuclear factor-1\u03b2 (HNF-1\u03b2), mutations of which produce kidney cysts. PDE4C is down-regulated and cAMP levels are increased in HNF-1\u03b2 mutant kidney cells and mice. Collectively, these findings identify PC2 and PDE4C as unique components of an AKAP complex in primary cilia and reveal a common mechanism for dysregulation of cAMP signaling in cystic kidney diseases arising from different gene mutations.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1016214108","type":"journal-article","created":{"date-parts":[[2011,6,14]],"date-time":"2011-06-14T14:03:48Z","timestamp":1308060228000},"page":"10679-10684","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":135,"title":["Polycystin-2 and phosphodiesterase 4C are components of a ciliary A-kinase anchoring protein complex that is disrupted in cystic kidney diseases"],"prefix":"10.1073","volume":"108","author":[{"given":"Yun-Hee","family":"Choi","sequence":"first","affiliation":[{"name":"Departments of aInternal Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Departments of aInternal Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachin","family":"Hajarnis","sequence":"additional","affiliation":[{"name":"Departments of aInternal Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhendong","family":"Ma","sequence":"additional","affiliation":[{"name":"Departments of aInternal Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah C.","family":"Chapin","sequence":"additional","affiliation":[{"name":"Departments of bCellular and Molecular Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Caplan","sequence":"additional","affiliation":[{"name":"Departments of bCellular and Molecular Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Pontoglio","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U567, Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche 8104, Universit\u00e9 Paris-Descartes, Institut Cochin, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Somlo","sequence":"additional","affiliation":[{"name":"Internal Medicine and Genetics, Yale University School of Medicine, New Haven, CT 06520; 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