{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:56:44Z","timestamp":1793692604699,"version":"4.5.1"},"update-to":[{"DOI":"10.1371\/journal.pgen.1012008","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000}}],"reference-count":87,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"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":["R01DK128089"],"award-info":[{"award-number":["R01DK128089"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive bilateral cyst formation. Multiple cellular pathways including second messenger cAMP signaling are dysregulated in ADPKD, but mechanisms initiating cysts are unknown. ADPKD is caused by mutations in\n                    <jats:italic>PKD1\/PKD2<\/jats:italic>\n                    genes encoding for polycystins that localize to primary cilia\u2014nonmotile, microtubule-based dynamic compartments sensing extracellular chemical\/mechanical signals. The compact cylindrical structure of cilia enables tunable signaling amplification regulatable by ciliary length. Severe cystogenesis from polycystin loss is cilia dependent and ciliary elongation is common in cystic epithelia. However, uncoupling the cilium-specific signals repressed by polycystins from downstream cystogenic pathways has proven challenging. Here we aim to understand roles of compartmentalized cAMP signaling in cystogenesis and ciliary length control. We investigated ANKMY2, an Ankyrin repeat MYND domain protein involved in maturation and ciliary localization of membrane adenylyl cyclases\u2014enzymes generating cAMP. In kidney-specific\n                    <jats:italic>Ankmy2\/Pkd1<\/jats:italic>\n                    knockout mice, loss of ANKMY2 suppressed early postnatal cystogenesis and significantly extended survival in an embryonic-onset\n                    <jats:italic>Pkd1<\/jats:italic>\n                    deletion model. Similarly, in an adult inducible\n                    <jats:italic>Pkd1<\/jats:italic>\n                    knockout model, ANKMY2 deficiency reduced cyst burden. Mechanistically, ANKMY2 controlled the ciliary trafficking of multiple adenylyl cyclases in mouse and human kidney epithelial cells without disrupting cilia while retaining cellular pools. Ciliary elongation began in dilatated tubules of adult onset ADPKD mice and further increased in cystic kidneys. Both initial and progressive phases of cilia lengthening were ANKMY2-dependent. Our findings indicate that ciliary adenylyl cyclase signaling likely promotes cilia-dependent cyst initiation distinct from cyst progression involving cellular cAMP. Importantly, kidneys lacking ANKMY2 did not show ciliary elongation despite elevated cAMP, suggesting that cilia lengthening during cyst progression could be contingent upon pre-cystic ciliary regulation. These results suggest a critical role for compartmentalized adenylyl cyclase signaling in ADPKD pathogenesis and a framework for identifying ciliary effectors and early subcellular events in cystogenesis.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1012008","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T18:52:22Z","timestamp":1767207142000},"page":"e1012008","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Lack of ANKMY2 suppresses kidney cystogenesis in embryonic- and adult-onset polycystic kidney disease"],"prefix":"10.1371","volume":"21","author":[{"given":"Sun-Hee","family":"Hwang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungsuk","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemant","family":"Badgandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin A.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen M.","family":"Woodward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4790-3090","authenticated-orcid":true,"given":"Saikat","family":"Mukhopadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"pgen.1012008.ref001","article-title":"Postnatal maturation of rabbit renal collecting duct. 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to kidney cilia and the ciliary level is elevated in orpk mice with polycystic kidney disease","volume":"12","author":"GJ Pazour","year":"2002","journal-title":"Curr Biol"},{"issue":"10","key":"pgen.1012008.ref009","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1097\/01.ASN.0000029587.47950.25","article-title":"The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia","volume":"13","author":"BK Yoder","year":"2002","journal-title":"J Am Soc Nephrol"},{"issue":"9","key":"pgen.1012008.ref010","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1038\/ng.2715","article-title":"Loss of cilia suppresses cyst growth in genetic models of autosomal dominant polycystic kidney disease","volume":"45","author":"M Ma","year":"2013","journal-title":"Nat Genet"},{"issue":"3","key":"pgen.1012008.ref011","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1042\/BST20231403","article-title":"Molecular and structural 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