{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:30:55Z","timestamp":1791286255929,"version":"4.1.0"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"47","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,11,20]]},"abstract":"<jats:p>\n                    Polycystin-1 (PC1) has an essential function in renal tubular morphogenesis and disruption of its function causes cystogenesis in human autosomal dominant polycystic kidney disease. We have previously shown that recombinant human PC1 is\n                    <jats:italic>cis<\/jats:italic>\n                    -autoproteolytically cleaved at the G protein-coupled receptor proteolytic site domain. To investigate the role of cleavage\n                    <jats:italic>in vivo<\/jats:italic>\n                    , we generated by gene targeting a\n                    <jats:italic>Pkd1<\/jats:italic>\n                    knockin mouse (\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>V\/V<\/jats:sup>\n                    ) that expresses noncleavable PC1. The\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>V\/V<\/jats:sup>\n                    mice show a hypomorphic phenotype, characterized by a delayed onset and distal nephron segment involvement of cystogenesis at postnatal maturation stage. We show that PC1 is ubiquitously and incompletely cleaved in wild-type mice, so that uncleaved and cleaved PC1 molecules coexist. Our study establishes a critical but restricted role of cleavage for PC1 function and suggests a differential function of the two types of PC1 molecules\n                    <jats:italic>in vivo<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1073\/pnas.0708217104","type":"journal-article","created":{"date-parts":[[2007,11,14]],"date-time":"2007-11-14T21:19:01Z","timestamp":1195075141000},"page":"18688-18693","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":170,"title":["Essential role of cleavage of Polycystin-1 at G protein-coupled receptor proteolytic site for kidney tubular structure"],"prefix":"10.1073","volume":"104","author":[{"given":"Shengqiang","family":"Yu","sequence":"first","affiliation":[{"name":"*Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Hackmann","sequence":"additional","affiliation":[{"name":"*Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobing","family":"He","sequence":"additional","affiliation":[{"name":"*Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Piontek","sequence":"additional","affiliation":[{"name":"*Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Garc\u00eda-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"*Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis F.","family":"Menezes","sequence":"additional","affiliation":[{"name":"*Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangxue","family":"Xu","sequence":"additional","affiliation":[{"name":"*Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory G.","family":"Germino","sequence":"additional","affiliation":[{"name":"*Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Qian","sequence":"additional","affiliation":[{"name":"*Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2007,11,20]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1053\/snep.2001.20929"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199307293290508"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1097-179"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.211191098"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.040550097"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000144204.01352.86"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s003359900429"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0695-151"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneph0070"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(99)80379-0"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-007-7067-1"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.252484899"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703218200"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.38.072902.093416"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI21753"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2005.12.005"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.20410"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-169X.2004.00729.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119090"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.11.1641"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e03-05-0296"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.12.6191"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1978.75"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80052-5"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.12.5096"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1177\/35.1.3794309"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1996.253"},{"key":"e_1_3_3_28_2","first-page":"757","volume":"30","author":"Hoyer JR","year":"1974","unstructured":"JR Hoyer, JS Resnick, AF Michael, RL Vernier Lab Invest 30, 757\u2013761 (1974).","journal-title":"Lab Invest"},{"key":"e_1_3_3_29_2","first-page":"F619","volume":"271","author":"Ecelbarger CA","year":"1996","unstructured":"CA Ecelbarger, J Terris, JR Hoyer, S Nielsen, JB Wade, MA Knepper Am J Physiol 271, F619\u2013F628 (1996).","journal-title":"Am J Physiol"},{"key":"e_1_3_3_30_2","first-page":"157","volume":"44","author":"Stange T","year":"2000","unstructured":"T Stange, U Kettmann, HJ Holzhausen Eur J Histochem 44, 157\u2013164 (2000).","journal-title":"Eur J Histochem"}],"updated-by":[{"DOI":"10.1073\/pnas.0711495105","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2008,1,29]],"date-time":"2008-01-29T00:00:00Z","timestamp":1201564800000}}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0708217104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T16:40:07Z","timestamp":1649781607000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0708217104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,11,20]]},"references-count":30,"journal-issue":{"issue":"47","published-print":{"date-parts":[[2007,11,20]]}},"alternative-id":["10.1073\/pnas.0708217104"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0708217104","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1097045.553015","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,11,20]]},"assertion":[{"value":"2007-08-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-11-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}