{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:16:25Z","timestamp":1789874185169,"version":"4.0.1"},"reference-count":110,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,26]],"date-time":"2020-09-26T00:00:00Z","timestamp":1601078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK080236"],"award-info":[{"award-number":["R01 DK080236"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>As a rare hereditary disease, congenital nephrogenic diabetes insipidus (NDI) is clinically characterized by polyuria with hyposthenuria and polydipsia. NDI results from collecting duct principal cell hyporesponsiveness or insensitivity to the antidiuretic action of arginine vasopressin (AVP). The principal cell-specific water channel aquaporin-2 (AQP2) plays an essential role in water reabsorption along osmotic gradients. The capacity to accumulate AQP2 in the apical plasma membrane in response to decreased fluid volume or increased plasma osmolality is critically regulated by the antidiuretic hormone AVP and its receptor 2 (AVPR2). Mutations in AVPR2 result in X-linked recessive NDI, the most common form of inherited NDI. Genetic defects in AQP2 cause autosomal recessive or dominant NDI. In this review, we provide an updated overview of the genetic and molecular mechanisms of congenital NDI, with a focus on the potential disease-causing mutations in AVPR2 and AQP2, the molecular defects in the AVPR2 and AQP2 mutants, post-translational modifications (i.e., phosphorylation, ubiquitination, and glycosylation) and various protein-protein interactions that regulate phosphorylation, ubiquitination, tetramerization, trafficking, stability, and degradation of AQP2.<\/jats:p>","DOI":"10.3390\/cells9102172","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T08:02:58Z","timestamp":1601280178000},"page":"2172","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["AQP2: Mutations Associated with Congenital Nephrogenic Diabetes Insipidus and Regulation by Post-Translational Modifications and Protein-Protein Interactions"],"prefix":"10.3390","volume":"9","author":[{"given":"Chao","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Regenerative &amp; Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Higgins","sequence":"additional","affiliation":[{"name":"Department of Regenerative &amp; Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Regenerative &amp; Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.semnephrol.2006.03.004","article-title":"Acquired nephrogenic diabetes insipidus","volume":"26","author":"Khanna","year":"2006","journal-title":"Semin. Nephrol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/978-3-319-51436-9_7","article-title":"Development and Diseases of the Collecting Duct System","volume":"60","author":"Chen","year":"2017","journal-title":"Results Probl. Cell Differ."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/ng1092-99","article-title":"Mutations in the vasopressin type 2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus","volume":"2","author":"Dreesen","year":"1992","journal-title":"Nat. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1126\/science.8140421","article-title":"Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine","volume":"264","author":"Deen","year":"1994","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1007\/s12020-008-9074-x","article-title":"Identification of two novel aquaporin-2 mutations in a Thai girl with congenital nephrogenic diabetes insipidus","volume":"33","author":"Sahakitrungruang","year":"2008","journal-title":"Endocrine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1007\/s10157-012-0726-z","article-title":"Hereditary nephrogenic diabetes insipidus in Japanese patients: Analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2","volume":"17","author":"Sasaki","year":"2013","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1093\/hmg\/6.11.1865","article-title":"Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response","volume":"6","author":"Canfield","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1113\/jphysiol.2010.187674","article-title":"New autosomal recessive mutations in aquaporin-2 causing nephrogenic diabetes insipidus through deficient targeting display normal expression in Xenopus oocytes","volume":"588","author":"Lussier","year":"2010","journal-title":"J. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1097\/01.ASN.0000027355.41663.14","article-title":"Cell-biologic and functional analyses of five new Aquaporin-2 missense mutations that cause recessive nephrogenic diabetes insipidus","volume":"13","author":"Marr","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2694","DOI":"10.1210\/jcem.87.6.8617","article-title":"Two novel aquaporin-2 mutations responsible for congenital nephrogenic diabetes insipidus in Chinese families","volume":"87","author":"Lin","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_11","first-page":"648","article-title":"Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene","volume":"55","author":"Verdijk","year":"1994","journal-title":"Am. J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1681\/ASN.V82242","article-title":"New mutations in the AQP2 gene in nephrogenic diabetes insipidus resulting in functional but misrouted water channels","volume":"8","author":"Mulders","year":"1997","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.3346\/jkms.2005.20.6.1076","article-title":"Two novel mutations in the aquaporin 2 gene in a girl with congenital nephrogenic diabetes insipidus","volume":"20","author":"Cheong","year":"2005","journal-title":"J. Korean Med. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/ckj\/sfs029","article-title":"Aquaporin-2: New mutations responsible for autosomal-recessive nephrogenic diabetes insipidus-update and epidemiology","volume":"5","author":"Bichet","year":"2012","journal-title":"Clin. Kidney J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1007\/s00431-015-2534-4","article-title":"Novel mutations associated with nephrogenic diabetes insipidus. A clinical-genetic study","volume":"174","author":"Madariaga","year":"2015","journal-title":"Eur. J. Pediatr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1515\/jpem-2013-0097","article-title":"Novel AQP2 mutation causing congenital nephrogenic diabetes insipidus: Challenges in management during infancy","volume":"27","author":"Rugpolmuang","year":"2014","journal-title":"J. Pediatric Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1097\/01.gim.0000223554.46981.7a","article-title":"Novel mutations underlying nephrogenic diabetes insipidus in Arab families","volume":"8","author":"Carroll","year":"2006","journal-title":"Genet. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1093\/ndt\/gfk024","article-title":"Nephrogenic diabetes insipidus, thiazide treatment and renal cell carcinoma","volume":"21","author":"Zaki","year":"2006","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"596","DOI":"10.3892\/br.2014.283","article-title":"Congenital nephrogenic diabetes insipidus with a novel mutation in the aquaporin 2 gene","volume":"2","author":"Park","year":"2014","journal-title":"Biomed. Rep."},{"key":"ref_20","first-page":"3205","article-title":"Novel mutations in aquaporin-2 gene in female siblings with nephrogenic diabetes insipidus: Evidence of disrupted water channel function","volume":"83","author":"Goji","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_21","first-page":"85","article-title":"Clinical overview of nephrogenic diabetes insipidus based on a nationwide survey in Japan","volume":"57","author":"Fujimoto","year":"2014","journal-title":"Yonago Acta Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1007\/s12020-012-9704-1","article-title":"Mutations in the AVPR2, AVP-NPII, and AQP2 genes in Turkish patients with diabetes insipidus","volume":"42","author":"Duzenli","year":"2012","journal-title":"Endocrine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"p33","DOI":"10.1159\/000098136","article-title":"Characterization of two novel missense mutations in the AQP2 gene causing nephrogenic diabetes insipidus","volume":"105","author":"Iolascon","year":"2007","journal-title":"Nephron Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1681\/ASN.V8121855","article-title":"Mutations in the vasopressin V2 receptor and aquaporin-2 genes in 12 families with congenital nephrogenic diabetes insipidus","volume":"8","author":"Forestier","year":"1997","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.semnephrol.2008.03.006","article-title":"Aquaporin 2 mutations in nephrogenic diabetes insipidus","volume":"28","author":"Loonen","year":"2008","journal-title":"Semin. Nephrol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"79","DOI":"10.6061\/clinics\/2012(01)13","article-title":"Novel compound aquaporin 2 mutations in nephrogenic diabetes insipidus","volume":"67","author":"Carneiro","year":"2012","journal-title":"Clin. (Sao Paulo)"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s004390050264","article-title":"Two novel mutations in the aquaporin-2 and the vasopressin V2 receptor genes in patients with congenital nephrogenic diabetes insipidus","volume":"98","author":"Oksche","year":"1996","journal-title":"Hum. Genet."},{"key":"ref_28","first-page":"3629","article-title":"Novel autosomal recessive gene mutations in aquaporin-2 in two Chinese congenital nephrogenic diabetes insipidus pedigrees","volume":"8","author":"Cen","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1507\/endocrj.K09E-078","article-title":"Novel mutation of aquaporin-2 gene in a patient with congenital nephrogenic diabetes insipidus","volume":"56","author":"Moon","year":"2009","journal-title":"Endocr. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"E891","DOI":"10.1002\/humu.21082","article-title":"p.R254Q mutation in the aquaporin-2 water channel causing dominant nephrogenic diabetes insipidus is due to a lack of arginine vasopressin-induced phosphorylation","volume":"30","author":"Savelkoul","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.1681\/ASN.2005010104","article-title":"Lack of arginine vasopressin-induced phosphorylation of aquaporin-2 mutant AQP2-R254L explains dominant nephrogenic diabetes insipidus","volume":"16","author":"Savelkoul","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Dollerup, P., Thomsen, T.M., Nejsum, L.N., Faerch, M., Osterbrand, M., Gregersen, N., Rittig, S., Christensen, J.H., and Corydon, T.J. (2015). Partial nephrogenic diabetes insipidus caused by a novel AQP2 variation impairing trafficking of the aquaporin-2 water channel. BMC Nephrol., 16.","DOI":"10.1186\/s12882-015-0213-3"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1172\/JCI2605","article-title":"An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic diabetes insipidus is retained in the Golgi complex","volume":"102","author":"Mulders","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_34","first-page":"686","article-title":"Autosomal recessive nephrogenic diabetes insipidus caused by an aquaporin-2 mutation","volume":"82","author":"Hochberg","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1507\/endocrj.50.473","article-title":"Two novel aquaporin-2 mutations in a sporadic Japanese patient with autosomal recessive nephrogenic diabetes insipidus","volume":"50","author":"Tajima","year":"2003","journal-title":"Endocr. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1086\/323643","article-title":"Three families with autosomal dominant nephrogenic diabetes insipidus caused by aquaporin-2 mutations in the C-terminus","volume":"69","author":"Kuwahara","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1093\/hmg\/11.7.779","article-title":"Heteroligomerization of an Aquaporin-2 mutant with wild-type Aquaporin-2 and their misrouting to late endosomes\/lysosomes explains dominant nephrogenic diabetes insipidus","volume":"11","author":"Marr","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1083\/jcb.200309017","article-title":"Reversed polarized delivery of an aquaporin-2 mutant causes dominant nephrogenic diabetes insipidus","volume":"163","author":"Kamsteeg","year":"2003","journal-title":"J Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"F1037","DOI":"10.1152\/ajprenal.00639.2012","article-title":"Inherited secondary nephrogenic diabetes insipidus: Concentrating on humans","volume":"304","author":"Bockenhauer","year":"2013","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.beem.2016.02.012","article-title":"Renal aquaporins and water balance disorders","volume":"30","author":"Moeller","year":"2016","journal-title":"Best Pr. Res. Clin. Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"R29","DOI":"10.1530\/EJE-20-0114","article-title":"GENETICS IN ENDOCRINOLOGY Pathophysiology, diagnosis and treatment of familial nephrogenic diabetes insipidus","volume":"183","author":"Bichet","year":"2020","journal-title":"Eur. J. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11663","DOI":"10.1073\/pnas.90.24.11663","article-title":"Cellular and subcellular immunolocalization of vasopressin-regulated water channel in rat kidney","volume":"90","author":"Nielsen","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","first-page":"F461","article-title":"Development of urinary concentrating capacity: Role of aquaporin-2","volume":"271","author":"Yasui","year":"1996","journal-title":"Am. J. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1046\/j.1523-1755.2001.00965.x","article-title":"Role of aquaporin-2 gene expression in hyponatremic rats with chronic vasopressin-induced antidiuresis","volume":"60","author":"Saito","year":"2001","journal-title":"Kidney Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"F881","DOI":"10.1152\/ajprenal.00367.2004","article-title":"Urea and urine concentrating ability: New insights from studies in mice","volume":"288","author":"Yang","year":"2005","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1681\/ASN.2004121079","article-title":"Vasopressin-V2 receptor stimulation reduces sodium excretion in healthy humans","volume":"16","author":"Bankir","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1146\/annurev-pharmtox-010919-023654","article-title":"Targeting the Trafficking of Kidney Water Channels for Therapeutic Benefit","volume":"60","author":"Cheung","year":"2020","journal-title":"Annu. Rev. Pharm. Toxicol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"F193","DOI":"10.1152\/ajprenal.00304.2019","article-title":"Aquaporins in the kidney: Physiology and pathophysiology","volume":"318","author":"Su","year":"2020","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1681\/ASN.2018030271","article-title":"Bile Acid G Protein-Coupled Membrane Receptor TGR5 Modulates Aquaporin 2-Mediated Water Homeostasis","volume":"29","author":"Li","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1124\/jpet.103.058008","article-title":"Rosiglitazone activates renal sodium- and water-reabsorptive pathways and lowers blood pressure in normal rats","volume":"308","author":"Song","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1159\/000373933","article-title":"Rosiglitazone promotes AQP2 plasma membrane expression in renal cells via a Ca-dependent\/cAMP-independent mechanism","volume":"35","author":"Procino","year":"2015","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Zhang, X.Y., Wang, B., and Guan, Y.F. (2016). Nuclear Receptor Regulation of Aquaporin-2 in the Kidney. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17071105"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"F305","DOI":"10.1152\/ajprenal.00685.2014","article-title":"Estradiol regulates AQP2 expression in the collecting duct: A novel inhibitory role for estrogen receptor alpha","volume":"309","author":"Cheema","year":"2015","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1681\/ASN.2005040371","article-title":"Molecular biology of hereditary diabetes insipidus","volume":"16","author":"Fujiwara","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"F257","DOI":"10.1152\/ajprenal.00491.2005","article-title":"Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus","volume":"291","author":"Robben","year":"2006","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1111\/j.1600-0854.2004.00239.x","article-title":"Disease-causing V(2) vasopressin receptors are retained in different compartments of the early secretory pathway","volume":"5","author":"Hermosilla","year":"2004","journal-title":"Traffic"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1111\/j.1600-0854.2004.00231.x","article-title":"A cure for traffic jams: Small molecule chaperones in the endoplasmic reticulum","volume":"5","author":"Romisch","year":"2004","journal-title":"Traffic"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1172\/JCI8688","article-title":"Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants","volume":"105","author":"Morello","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1681\/ASN.2005080854","article-title":"Pharmacologic chaperones as a potential treatment for X-linked nephrogenic diabetes insipidus","volume":"17","author":"Bernier","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1172\/JCI117920","article-title":"Water channels encoded by mutant aquaporin-2 genes in nephrogenic diabetes insipidus are impaired in their cellular routing","volume":"95","author":"Deen","year":"1995","journal-title":"J. Clin. Investig."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1681\/ASN.V76836","article-title":"Urinary content of aquaporin 1 and 2 in nephrogenic diabetes insipidus","volume":"7","author":"Deen","year":"1996","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1172\/JCI2303","article-title":"Defective aquaporin-2 trafficking in nephrogenic diabetes insipidus and correction by chemical chaperones","volume":"101","author":"Tamarappoo","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"215","DOI":"10.2169\/internalmedicine.37.215","article-title":"Aquaporin-2, a vasopressin-sensitive water channel, and nephrogenic diabetes insipidus","volume":"37","author":"Kuwahara","year":"1998","journal-title":"Intern. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3045","DOI":"10.1093\/hmg\/ddh339","article-title":"A novel mechanism in recessive nephrogenic diabetes insipidus: Wild-type aquaporin-2 rescues the apical membrane expression of intracellularly retained AQP2-P262L","volume":"13","author":"Savelkoul","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1093\/emboj\/18.9.2394","article-title":"An impaired routing of wild-type aquaporin-2 after tetramerization with an aquaporin-2 mutant explains dominant nephrogenic diabetes insipidus","volume":"18","author":"Kamsteeg","year":"1999","journal-title":"EMBO J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"F893","DOI":"10.1152\/ajprenal.00387.2002","article-title":"The ins and outs of aquaporin-2 trafficking","volume":"284","author":"Brown","year":"2003","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1681\/ASN.2009121267","article-title":"Calcitonin has a vasopressin-like effect on aquaporin-2 trafficking and urinary concentration","volume":"22","author":"Bouley","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"12949","DOI":"10.1073\/pnas.1104691108","article-title":"Vasopressin-independent targeting of aquaporin-2 by selective E-prostanoid receptor agonists alleviates nephrogenic diabetes insipidus","volume":"108","author":"Olesen","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6129","DOI":"10.1096\/fj.201902982R","article-title":"PKA-independent vasopressin signaling in renal collecting duct","volume":"34","author":"Datta","year":"2020","journal-title":"FASEB J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1096\/fj.02-0870fje","article-title":"Ser-256 phosphorylation dynamics of Aquaporin 2 during maturation from the ER to the vesicular compartment in renal cells","volume":"17","author":"Procino","year":"2003","journal-title":"FASEB J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"14800","DOI":"10.1074\/jbc.272.23.14800","article-title":"Phosphorylation of serine 256 is required for cAMP-dependent regulatory exocytosis of the aquaporin-2 water channel","volume":"272","author":"Fushimi","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_72","first-page":"F817","article-title":"Protein kinase A phosphorylation is involved in regulated exocytosis of aquaporin-2 in transfected LLC-PK1 cells","volume":"272","author":"Katsura","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"6952","DOI":"10.1073\/pnas.0602087103","article-title":"Congenital progressive hydronephrosis (cph) is caused by an S256L mutation in aquaporin-2 that affects its phosphorylation and apical membrane accumulation","volume":"103","author":"McDill","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7159","DOI":"10.1073\/pnas.0600895103","article-title":"Quantitative phosphoproteomics of vasopressin-sensitive renal cells: Regulation of aquaporin-2 phosphorylation at two sites","volume":"103","author":"Hoffert","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"24617","DOI":"10.1074\/jbc.M803074200","article-title":"Vasopressin-stimulated increase in phosphorylation at Ser269 potentiates plasma membrane retention of aquaporin-2","volume":"283","author":"Hoffert","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"F691","DOI":"10.1152\/ajprenal.00284.2006","article-title":"Dynamics of aquaporin-2 serine-261 phosphorylation in response to short-term vasopressin treatment in collecting duct","volume":"292","author":"Hoffert","year":"2007","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1073\/pnas.0910683107","article-title":"Phosphorylation of aquaporin-2 regulates its endocytosis and protein-protein interactions","volume":"107","author":"Moeller","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"18344","DOI":"10.1073\/pnas.0604073103","article-title":"Short-chain ubiquitination mediates the regulated endocytosis of the aquaporin-2 water channel","volume":"103","author":"Kamsteeg","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"F883","DOI":"10.1152\/ajprenal.00117.2011","article-title":"E3 ubiquitin-protein ligases in rat kidney collecting duct: Response to vasopressin stimulation and withdrawal","volume":"301","author":"Lee","year":"2011","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1152\/physiolgenomics.00031.2016","article-title":"Comprehensive database of human E3 ubiquitin ligases: Application to aquaporin-2 regulation","volume":"48","author":"Medvar","year":"2016","journal-title":"Physiol Genom."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Trimpert, C., Wesche, D., de Groot, T., Pimentel Rodriguez, M.M., Wong, V., van den Berg, D.T.M., Cheval, L., Ariza, C.A., Doucet, A., and Stagljar, I. (2017). NDFIP allows NEDD4\/NEDD4L-induced AQP2 ubiquitination and degradation. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0183774"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.molcel.2007.11.019","article-title":"The age of crosstalk: Phosphorylation, ubiquitination, and beyond","volume":"28","author":"Hunter","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_83","first-page":"3174","article-title":"Phosphorylation and ubiquitylation are opposing processes that regulate endocytosis of the water channel aquaporin-2","volume":"127","author":"Moeller","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"6833","DOI":"10.1021\/bi972217k","article-title":"The amino acid following an asn-X-Ser\/Thr sequon is an important determinant of N-linked core glycosylation efficiency","volume":"37","author":"Mellquist","year":"1998","journal-title":"Biochemistry"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1681\/ASN.V991553","article-title":"Glycosylation is not essential for vasopressin-dependent routing of aquaporin-2 in transfected Madin-Darby canine kidney cells","volume":"9","author":"Baumgarten","year":"1998","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1074\/jbc.M310767200","article-title":"Glycosylation is important for cell surface expression of the water channel aquaporin-2 but is not essential for tetramerization in the endoplasmic reticulum","volume":"279","author":"Hendriks","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nrm1052","article-title":"Quality control in the endoplasmic reticulum","volume":"4","author":"Ellgaard","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1681\/ASN.2008060648","article-title":"LIP5 interacts with aquaporin 2 and facilitates its lysosomal degradation","volume":"20","author":"Boone","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1267\/ahc.12003","article-title":"Close association of aquaporin-2 internalization with caveolin-1","volume":"45","author":"Aoki","year":"2012","journal-title":"Acta Histochem. Et Cytochem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"16696","DOI":"10.1073\/pnas.0708023104","article-title":"MAL decreases the internalization of the aquaporin-2 water channel","volume":"104","author":"Kamsteeg","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.febslet.2004.05.021","article-title":"Aquaporin-2 trafficking is regulated by PDZ-domain containing protein SPA-1","volume":"568","author":"Noda","year":"2004","journal-title":"Febs Lett."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.bbrc.2005.03.079","article-title":"Identification of a multiprotein \"motor\" complex binding to water channel aquaporin-2","volume":"330","author":"Noda","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"28721","DOI":"10.1074\/jbc.M611101200","article-title":"Heat shock protein 70 interacts with aquaporin-2 and regulates its trafficking","volume":"282","author":"Lu","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1021\/pr800894p","article-title":"Identification of phosphorylation-dependent binding partners of aquaporin-2 using protein mass spectrometry","volume":"8","author":"Zwang","year":"2009","journal-title":"J. Proteome Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1038\/ki.2008.402","article-title":"AKAP220 colocalizes with AQP2 in the inner medullary collecting ducts","volume":"74","author":"Okutsu","year":"2008","journal-title":"Kidney Int."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2914","DOI":"10.1242\/jcs.204842","article-title":"Ezrin directly interacts with AQP2 and promotes its endocytosis","volume":"130","author":"Li","year":"2017","journal-title":"J. Cell Sci."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Wu, H., Chen, L., Zhang, X., Zhou, Q., Li, J.M., Berger, S., Borok, Z., Zhou, B., Xiao, Z., and Yin, H. (2013). Aqp5 is a new transcriptional target of dot1a and a regulator of aqp2. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053342"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.bbrc.2004.07.195","article-title":"Water channel aquaporin-2 directly binds to actin","volume":"322","author":"Noda","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"F956","DOI":"10.1152\/ajprenal.00297.2019","article-title":"Rab7 involves Vps35 to mediate AQP2 sorting and apical trafficking in collecting duct cells","volume":"318","author":"Wang","year":"2020","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Murali, S.K., Aroankins, T.S., Moeller, H.B., and Fenton, R.A. (2019). The Deubiquitylase USP4 Interacts with the Water Channel AQP2 to Modulate Its Apical Membrane Accumulation and Cellular Abundance. Cells, 8.","DOI":"10.3390\/cells8030265"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Choi, H.J., Jang, H.J., Park, E., Tingskov, S.J., Norregaard, R., Jung, H.J., and Kwon, T.H. (2020). Sorting Nexin 27 Regulates the Lysosomal Degradation of Aquaporin-2 Protein in the Kidney Collecting Duct. Cells, 9.","DOI":"10.3390\/cells9051208"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1074\/jbc.M115.691121","article-title":"Regulation of the Water Channel Aquaporin-2 via 14-3-3theta and -zeta","volume":"291","author":"Moeller","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1038\/s41467-018-03771-2","article-title":"AKAPs-PKA disruptors increase AQP2 activity independently of vasopressin in a model of nephrogenic diabetes insipidus","volume":"9","author":"Ando","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/nrm1469","article-title":"From structure to disease: The evolving tale of aquaporin biology","volume":"5","author":"King","year":"2004","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1007\/s00335-007-9041-5","article-title":"Comparative functional analysis of aquaporins\/glyceroporins in mammals and anurans","volume":"18","author":"Krane","year":"2007","journal-title":"Mamm. Genome"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1074\/jbc.270.4.1908","article-title":"Molecular cloning and characterization of an aquaporin cDNA from salivary, lacrimal, and respiratory tissues","volume":"270","author":"Raina","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/S0140-6736(00)04140-4","article-title":"Defective cellular trafficking of lacrimal gland aquaporin-5 in Sjogren\u2019s syndrome","volume":"357","author":"Tsubota","year":"2001","journal-title":"Lancet"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1007\/s003359901030","article-title":"Cloning and characterization of murine Aqp5: Evidence for a conserved aquaporin gene cluster","volume":"10","author":"Krane","year":"1999","journal-title":"Mamm. Genome"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1681\/ASN.2012080866","article-title":"Aqp2-expressing cells give rise to renal intercalated cells","volume":"24","author":"Wu","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"C99","DOI":"10.1152\/ajpcell.00082.2017","article-title":"Identification of UT-A1- and AQP2-interacting proteins in rat inner medullary collecting duct","volume":"314","author":"Chou","year":"2018","journal-title":"Am. J. Physiol. Cell Physiol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/10\/2172\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:13:55Z","timestamp":1760177635000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/10\/2172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,26]]},"references-count":110,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["cells9102172"],"URL":"https:\/\/doi.org\/10.3390\/cells9102172","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,26]]}}}