{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:44:54Z","timestamp":1789541094202,"version":"build-2803163510"},"reference-count":61,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,13]],"date-time":"2020-05-13T00:00:00Z","timestamp":1589328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2014R1A5A2009242; 2017R1D1A3B03032262; 2019R1A2C1007753"],"award-info":[{"award-number":["2014R1A5A2009242; 2017R1D1A3B03032262; 2019R1A2C1007753"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002739","name":"Aarhus Universitets Forskningsfond","doi-asserted-by":"publisher","award":["AUFF-E-2015-FLS8-69"],"award-info":[{"award-number":["AUFF-E-2015-FLS8-69"]}],"id":[{"id":"10.13039\/501100002739","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Danish Council for Independent Research \u2013 Medical Sciences","award":["6110-00231B"],"award-info":[{"award-number":["6110-00231B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Sorting nexin 27 (SNX27), a PDZ (Postsynaptic density-95\/Discs large\/Zonula occludens 1) domain-containing protein, cooperates with a retromer complex, which regulates intracellular trafficking and the abundance of membrane proteins. Since the carboxyl terminus of aquaporin-2 (AQP2c) has a class I PDZ-interacting motif (X-T\/S-X-\u03a6), the role of SNX27 in the regulation of AQP2 was studied. Co-immunoprecipitation assay of the rat kidney demonstrated an interaction of SNX27 with AQP2. Glutathione S-transferase (GST) pull-down assays revealed an interaction of the PDZ domain of SNX27 with AQP2c. Immunocytochemistry of HeLa cells co-transfected with FLAG-SNX27 and hemagglutinin (HA)-AQP2 also revealed co-localization throughout the cytoplasm. When the PDZ domain was deleted, punctate HA-AQP2 labeling was localized in the perinuclear region. The labeling was intensively overlaid by Lysotracker staining but not by GM130 labeling, a cis-Golgi marker. In rat kidneys and primary cultured inner medullary collecting duct cells, the subcellular redistribution of SNX27 was similar to AQP2 under 1-deamino-8-D-arginine vasopressin (dDAVP) stimulation\/withdrawal. Cell surface biotinylation assay showed that dDAVP-induced AQP2 translocation to the apical plasma membrane was unaffected after SNX27 knockdown in mpkCCD cells. In contrast, the dDAVP-induced AQP2 protein abundance was significantly attenuated without changes in AQP2 mRNA expression. Moreover, the AQP2 protein abundance was markedly declined during the dDAVP withdrawal period after stimulation under SNX27 knockdown, which was inhibited by lysosome inhibitors. Autophagy was induced after SNX27 knockdown in mpkCCD cells. Lithium-induced nephrogenic diabetes insipidus in rats revealed a significant downregulation of SNX27 in the kidney inner medulla. Taken together, the PDZ domain-containing SNX27 interacts with AQP2 and depletion of SNX27 contributes to the autophagy-lysosomal degradation of AQP2.<\/jats:p>","DOI":"10.3390\/cells9051208","type":"journal-article","created":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T02:55:41Z","timestamp":1589424941000},"page":"1208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Sorting Nexin 27 Regulates the Lysosomal Degradation of Aquaporin-2 Protein in the Kidney Collecting Duct"],"prefix":"10.3390","volume":"9","author":[{"given":"Hyo-Jung","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu 41944, Korea"},{"name":"New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Taegu 41061, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo-Ju","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu 41944, Korea"},{"name":"BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Taegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Euijung","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu 41944, Korea"},{"name":"BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Taegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stine Julie","family":"Tingskov","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University, Aarhus 8200, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke","family":"N\u00f8rregaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University, Aarhus 8200, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Jun","family":"Jung","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1561-6508","authenticated-orcid":false,"given":"Tae-Hwan","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu 41944, Korea"},{"name":"BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Taegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"F1318","DOI":"10.1152\/ajprenal.00485.2016","article-title":"Molecular mechanisms regulating aquaporin-2 in kidney collecting duct","volume":"311","author":"Jung","year":"2016","journal-title":"Am. 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