{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:10:41Z","timestamp":1779149441353,"version":"3.51.4"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81771240"],"award-info":[{"award-number":["81771240"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Australian National Health and Medical Research Council","award":["APP1124011"],"award-info":[{"award-number":["APP1124011"]}]},{"DOI":"10.13039\/501100001030","name":"National Heart Foundation of Australia","doi-asserted-by":"crossref","award":["101856"],"award-info":[{"award-number":["101856"]}],"id":[{"id":"10.13039\/501100001030","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,22]]},"abstract":"<jats:p>\n                    <jats:italic>PDCD10<\/jats:italic>\n                    , also known as\n                    <jats:italic>CCM3<\/jats:italic>\n                    , is a gene found to be associated with the human disease cerebral cavernous malformations (CCMs). PDCD10 forms a complex with GCKIII kinases including STK24, STK25, and MST4. Studies in\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>elegans<\/jats:italic>\n                    and\n                    <jats:italic>Drosophila<\/jats:italic>\n                    have shown a pivotal role of the PDCD10-GCKIII complex in maintaining epithelial integrity. Here, we found that mice deficient of\n                    <jats:italic>Pdcd10<\/jats:italic>\n                    or\n                    <jats:italic>Stk24\/25<\/jats:italic>\n                    in the kidney tubules developed polyuria and displayed increased water consumption. Although the expression levels of aquaporin genes were not decreased, the levels of total and phosphorylated aquaporin 2 (Aqp2) protein in the apical membrane of tubular epithelial cells were decreased in\n                    <jats:italic>Pdcd10<\/jats:italic>\n                    - and\n                    <jats:italic>Stk24\/25<\/jats:italic>\n                    -deficient mice. This loss of Aqp2 was associated with increased expression and membrane targeting of Ezrin and phosphorylated Ezrin, Radixin, Moesin (p-ERM) proteins and impaired intracellular vesicle trafficking. Treatment with Erlotinib, a tyrosine kinase inhibitor promoting exocytosis and inhibiting endocytosis, normalized the expression level and membrane abundance of Aqp2 protein, and partially rescued the water reabsorption defect observed in the Pdcd10-deficient mice. Our current study identified the PDCD10-STK-ERM signaling pathway as a potentially novel pathway required for water balance control by regulating vesicle trafficking and protein abundance of AQP2 in the kidneys.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.142838","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T14:01:31Z","timestamp":1624284091000},"source":"Crossref","is-referenced-by-count":19,"title":["Pdcd10-Stk24\/25 complex controls kidney water reabsorption by regulating Aqp2 membrane targeting"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1966-0485","authenticated-orcid":true,"given":"Rui","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi-Ting","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yude","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0135-8632","authenticated-orcid":true,"given":"Jaesung P.","family":"Choi","sequence":"additional","affiliation":[{"name":"Lab of Cardiovascular Signaling, Centenary Institute, and Sydney Medical School, University of Sydney, Sydney, 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