{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:36:10Z","timestamp":1787002570266,"version":"build-2736575974"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T00:00:00Z","timestamp":1480291200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T00:00:00Z","timestamp":1480291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Heritable nephrogenic diabetes insipidus (NDI) is characterized by defective urine concentration mechanisms in the kidney, which are mainly caused by loss-of-function mutations in the vasopressin type 2 receptor. For the treatment of heritable NDI, novel strategies that bypass the defective vasopressin type 2 receptor are required to activate the aquaporin-2 (AQP2) water channel. Here we show that Wnt5a regulates AQP2 protein expression, phosphorylation and trafficking, suggesting that Wnt5a is an endogenous ligand that can regulate AQP2 without the activation of the classic vasopressin\/cAMP signalling pathway. Wnt5a successfully increases the apical membrane localization of AQP2 and urine osmolality in an NDI mouse model. We also demonstrate that calcineurin is a key regulator of Wnt5a-induced AQP2 activation without affecting intracellular cAMP level and PKA activity. The importance of calcineurin is further confirmed with its activator, arachidonic acid, which shows vasopressin-like effects underlining that calcineurin activators may be potential therapeutic targets for heritable NDI.<\/jats:p>","DOI":"10.1038\/ncomms13636","type":"journal-article","created":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T05:52:10Z","timestamp":1480312330000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Wnt5a induces renal AQP2 expression by activating calcineurin signalling pathway"],"prefix":"10.1038","volume":"7","author":[{"given":"Fumiaki","family":"Ando","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eisei","family":"Sohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuji","family":"Morimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naofumi","family":"Yui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohiro","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eriko","family":"Kikuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiei","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayasu","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Vandewalle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatemitsu","family":"Rai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sei","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Uchida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,11,28]]},"reference":[{"key":"BFncomms13636_CR1","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1210\/er.2012-1044","volume":"34","author":"HB Moeller","year":"2013","unstructured":"Moeller, H. B., Rittig, S. & Fenton, R. A. Nephrogenic diabetes insipidus: essential insights into the molecular background and potential therapies for treatment. Endocr. Rev. 34, 278\u2013301 (2013).","journal-title":"Endocr. Rev."},{"key":"BFncomms13636_CR2","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/BF02549772","volume":"22","author":"T Nakada","year":"1990","unstructured":"Nakada, T., Miyauchi, T., Sumiya, H. & Shimazaki, J. Nonobstructive urinary tract dilatation in nephrogenic diabetes insipidus. Int. Urol. Nephrol. 22, 419\u2013427 (1990).","journal-title":"Int. Urol. Nephrol."},{"key":"BFncomms13636_CR3","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1053\/j.ackd.2006.01.006","volume":"13","author":"DG Bichet","year":"2006","unstructured":"Bichet, D. G. Nephrogenic diabetes insipidus. Adv. Chronic Kidney Dis. 13, 96\u2013104 (2006).","journal-title":"Adv. Chronic Kidney Dis."},{"key":"BFncomms13636_CR4","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1007\/s10157-012-0726-z","volume":"17","author":"S Sasaki","year":"2013","unstructured":"Sasaki, S., Chiga, M., Kikuchi, E., Rai, T. & Uchida, S. Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2. Clin. Exp. Nephrol. 17, 338\u2013344 (2013).","journal-title":"Clin. Exp. Nephrol."},{"key":"BFncomms13636_CR5","doi-asserted-by":"publisher","first-page":"F935","DOI":"10.1152\/ajprenal.00559.2015","volume":"311","author":"ET Olesen","year":"2016","unstructured":"Olesen, E. T., Moeller, H. B., Assentoft, M., MacAulay, N. & Fenton, R. A. The vasopressin type-2 receptor and prostaglandin receptors EP2 and EP4 can increase aquaporin-2 plasma membrane targeting through a cAMP independent pathway. Am. J. Physiol. Renal Physiol. 311, F935\u2013F944 (2016).","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"BFncomms13636_CR6","doi-asserted-by":"publisher","first-page":"2","DOI":"10.4172\/2157-7412.1000225","volume":"5","author":"G Procino","year":"2014","unstructured":"Procino, G., Milano, S., Carmosino, M., Gerbino, A. & Bonfrate, L. Hereditary nephrogenic diabetes insipidus: molecular basis of the defect and potential novel strategies for treatment. J. Genet. Syndr. Gene Ther. 5, 2 (2014).","journal-title":"J. Genet. Syndr. Gene Ther."},{"key":"BFncomms13636_CR7","doi-asserted-by":"publisher","first-page":"3115","DOI":"10.1172\/JCI39680","volume":"119","author":"JH Li","year":"2009","unstructured":"Li, J. H. et al. A selective EP4 PGE2 receptor agonist alleviates disease in a new mouse model of X-linked nephrogenic diabetes insipidus. J. Clin. Invest. 119, 3115\u20133126 (2009).","journal-title":"J. Clin. Invest."},{"key":"BFncomms13636_CR8","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1681\/ASN.2009121267","volume":"22","author":"R Bouley","year":"2011","unstructured":"Bouley, R. et al. Calcitonin has a vasopressin-like effect on aquaporin-2 trafficking and urinary concentration. J. Am. Soc. Nephrol. 22, 59\u201372 (2011).","journal-title":"J. Am. Soc. Nephrol."},{"key":"BFncomms13636_CR9","doi-asserted-by":"publisher","first-page":"12949","DOI":"10.1073\/pnas.1104691108","volume":"108","author":"ET Olesen","year":"2011","unstructured":"Olesen, E. T., R\u00fctzler, M. R., Moeller, H. B., Praetorius, H. A. & Fenton, R. A. Vasopressin-independent targeting of aquaporin-2 by selective E-prostanoid receptor agonists alleviates nephrogenic diabetes insipidus. Proc. Natl Acad. Sci. USA 108, 12949\u201312954 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms13636_CR10","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/ki.2014.10","volume":"86","author":"G Procino","year":"2014","unstructured":"Procino, G. et al. Combination of secretin and fluvastatin ameliorates the polyuria associated with X-linked nephrogenic diabetes insipidus in mice. Kidney Int. 86, 127\u2013138 (2014).","journal-title":"Kidney Int."},{"key":"BFncomms13636_CR11","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1172\/JCI9594","volume":"106","author":"R Bouley","year":"2000","unstructured":"Bouley, R. et al. Nitric oxide and atrial natriuretic factor stimulate cGMP-dependent membrane insertion of aquaporin 2 in renal epithelial cells. J. Clin. Invest. 106, 1115\u20131126 (2000).","journal-title":"J. Clin. Invest."},{"key":"BFncomms13636_CR12","doi-asserted-by":"publisher","first-page":"F309","DOI":"10.1152\/ajprenal.00001.2011","volume":"301","author":"W Li","year":"2011","unstructured":"Li, W. et al. Simvastatin enhances aquaporin-2 surface expression and urinary concentration in vasopressin-deficient Brattleboro rats through modulation of Rho GTPase. Am. J. Physiol. Renal Physiol. 301, F309\u2013F318 (2011).","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"BFncomms13636_CR13","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1007\/s00424-011-1007-5","volume":"462","author":"G Procino","year":"2011","unstructured":"Procino, G. et al. Fluvastatin modulates renal water reabsorption in vivo through increased AQP2 availability at the apical plasma membrane of collecting duct cells. Pflugers Arch. 462, 753\u2013766 (2011).","journal-title":"Pflugers Arch."},{"key":"BFncomms13636_CR14","doi-asserted-by":"publisher","first-page":"C597","DOI":"10.1152\/ajpcell.00154.2014","volume":"307","author":"N Nomura","year":"2014","unstructured":"Nomura, N. et al. High-throughput chemical screening identifies AG-490 as a stimulator of aquaporin 2 membrane expression and urine concentration. Am. J. Physiol. Cell Physiol. 307, C597\u2013C605 (2014).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"BFncomms13636_CR15","doi-asserted-by":"publisher","first-page":"13624","DOI":"10.1074\/jbc.M500040200","volume":"280","author":"JD Hoffert","year":"2005","unstructured":"Hoffert, J. D., Chou, C. L., Fenton, R. A. & Knepper, M. A. Calmodulin is required for vasopressin-stimulated increase in cyclic AMP production in inner medullary collecting duct. J. Biol. Chem. 280, 13624\u201313630 (2005).","journal-title":"J. Biol. Chem."},{"key":"BFncomms13636_CR16","doi-asserted-by":"publisher","first-page":"F882","DOI":"10.1152\/ajprenal.00411.2005","volume":"291","author":"KP Yip","year":"2006","unstructured":"Yip, K. P. Epac-mediated Ca(2+) mobilization and exocytosis in inner medullary collecting duct. Am. J. Physiol. Renal Physiol. 291, F882\u2013F890 (2006).","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"BFncomms13636_CR17","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1093\/abbs\/gmr079","volume":"43","author":"A De","year":"2011","unstructured":"De, A. Wnt\/Ca2+ signaling pathway: a brief overview. Acta Biochim. Biophys. Sin. 43, 745\u2013756 (2011).","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"BFncomms13636_CR18","doi-asserted-by":"publisher","first-page":"2144","DOI":"10.1038\/sj.onc.1208370","volume":"24","author":"N Kremenevskaja","year":"2005","unstructured":"Kremenevskaja, N. et al. Wnt-5a has tumor suppressor activity in thyroid carcinoma. Oncogene 24, 2144\u20132154 (2005).","journal-title":"Oncogene"},{"key":"BFncomms13636_CR19","doi-asserted-by":"publisher","first-page":"6024","DOI":"10.1128\/MCB.02354-05","volume":"26","author":"J Dejmek","year":"2006","unstructured":"Dejmek, J., S\u00e4fholm, A., Kamp Nielsen, C., Andersson, T. & Leandersson, K. Wnt-5a\/Ca2+-induced NFAT activity is counteracted by Wnt-5a\/Yes-Cdc42-casein kinase 1alpha signaling in human mammary epithelial cells. Mol. Cell Biol. 26, 6024\u20136036 (2006).","journal-title":"Mol. Cell Biol."},{"key":"BFncomms13636_CR20","doi-asserted-by":"publisher","first-page":"30990","DOI":"10.1074\/jbc.M603603200","volume":"281","author":"L Ma","year":"2006","unstructured":"Ma, L. & Wang, H. Y. Suppression of cyclic GMP-dependent protein kinase is essential to the Wnt\/cGMP\/Ca2+ pathway. J. Biol. Chem. 281, 30990\u201331001 (2006).","journal-title":"J. Biol. Chem."},{"key":"BFncomms13636_CR21","doi-asserted-by":"publisher","first-page":"2740","DOI":"10.1074\/jbc.M508386200","volume":"281","author":"A S\u00e4fholm","year":"2006","unstructured":"S\u00e4fholm, A. et al. A formylated hexapeptide ligand mimics the ability of Wnt-5a to impair migration of human breast epithelial cells. J. Biol. Chem. 281, 2740\u20132749 (2006).","journal-title":"J. Biol. Chem."},{"key":"BFncomms13636_CR22","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/dvdy.22156","volume":"239","author":"AD Person","year":"2010","unstructured":"Person, A. D. et al. WNT5A mutations in patients with autosomal dominant Robinow syndrome. Dev. Dyn. 239, 327\u2013337 (2010).","journal-title":"Dev. Dyn."},{"key":"BFncomms13636_CR23","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1046\/j.1365-2443.2003.00662.x","volume":"8","author":"I Oishi","year":"2003","unstructured":"Oishi, I. et al. The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a\/JNK signalling pathway. Genes Cells 8, 645\u2013654 (2003).","journal-title":"Genes Cells"},{"key":"BFncomms13636_CR24","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1111\/j.1748-1716.2011.02294.x","volume":"204","author":"A Kikuchi","year":"2012","unstructured":"Kikuchi, A., Yamamoto, H., Sato, A. & Matsumoto, S. Wnt5a: its signalling, functions and implication in diseases. Acta Physiol. 204, 17\u201333 (2012).","journal-title":"Acta Physiol."},{"key":"BFncomms13636_CR25","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1681\/ASN.V105923","volume":"10","author":"M Bens","year":"1999","unstructured":"Bens, M. et al. Corticosteroid-dependent sodium transport in a novel immortalized mouse collecting duct principal cell line. J. Am. Soc. Nephrol. 10, 923\u2013934 (1999).","journal-title":"J. Am. Soc. Nephrol."},{"key":"BFncomms13636_CR26","doi-asserted-by":"publisher","first-page":"10379","DOI":"10.1074\/jbc.M111880200","volume":"277","author":"U Hasler","year":"2002","unstructured":"Hasler, U. et al. Long term regulation of aquaporin-2 expression in vasopressin-responsive renal collecting duct principal cells. J. Biol. Chem. 277, 10379\u201310386 (2002).","journal-title":"J. Biol. Chem."},{"key":"BFncomms13636_CR27","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1681\/ASN.2008060566","volume":"20","author":"W He","year":"2009","unstructured":"He, W. et al. Wnt\/beta-catenin signaling promotes renal interstitial fibrosis. J. Am. Soc. Nephrol. 20, 765\u2013776 (2009).","journal-title":"J. Am. Soc. Nephrol."},{"key":"BFncomms13636_CR28","doi-asserted-by":"publisher","first-page":"14800","DOI":"10.1074\/jbc.272.23.14800","volume":"272","author":"K Fushimi","year":"1997","unstructured":"Fushimi, K., Sasaki, S. & Marumo, F. Phosphorylation of serine 256 is required for cAMP-dependent regulatory exocytosis of the aquaporin-2 water channel. J. Biol. Chem. 272, 14800\u201314804 (1997).","journal-title":"J. Biol. Chem."},{"key":"BFncomms13636_CR29","doi-asserted-by":"publisher","first-page":"C636","DOI":"10.1152\/ajpcell.00433.2009","volume":"300","author":"G Tamma","year":"2011","unstructured":"Tamma, G., Robben, J. H., Trimpert, C., Boone, M. & Deen, P. M. Regulation of AQP2 localization by S256 and S261 phosphorylation and ubiquitination. Am. J. Physiol. Cell Physiol. 300, C636\u2013C646 (2011).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"BFncomms13636_CR30","doi-asserted-by":"publisher","first-page":"24617","DOI":"10.1074\/jbc.M803074200","volume":"283","author":"JD Hoffert","year":"2008","unstructured":"Hoffert, J. D. et al. Vasopressin-stimulated increase in phosphorylation at Ser269 potentiates plasma membrane retention of aquaporin-2. J. Biol. Chem. 283, 24617\u201324627 (2008).","journal-title":"J. Biol. Chem."},{"key":"BFncomms13636_CR31","doi-asserted-by":"publisher","first-page":"35651","DOI":"10.1074\/jbc.M112.437913","volume":"288","author":"C Thrasivoulou","year":"2013","unstructured":"Thrasivoulou, C., Millar, M. & Ahmed, A. Activation of intracellular calcium by multiple Wnt ligands and translocation of \u03b2-catenin into the nucleus: a convergent model of Wnt\/Ca2+ and Wnt\/\u03b2-catenin pathways. J. Biol. Chem. 288, 35651\u201335659 (2013).","journal-title":"J. Biol. Chem."},{"key":"BFncomms13636_CR32","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/ki.2008.505","volume":"75","author":"HB Moeller","year":"2009","unstructured":"Moeller, H. B., Knepper, M. A. & Fenton, R. A. Serine 269 phosphorylated aquaporin-2 is targeted to the apical membrane of collecting duct principal cells. Kidney Int. 75, 295\u2013303 (2009).","journal-title":"Kidney Int."},{"key":"BFncomms13636_CR33","doi-asserted-by":"publisher","first-page":"C1606","DOI":"10.1152\/ajpcell.00588.2005","volume":"292","author":"SZ Li","year":"2007","unstructured":"Li, S. Z. et al. Calcineurin-NFATc signaling pathway regulates AQP2 expression in response to calcium signals and osmotic stress. Am. J. Physiol. Cell Physiol. 292, C1606\u2013C1616 (2007).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"BFncomms13636_CR34","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1097\/MNH.0b013e3283094eb1","volume":"17","author":"D Brown","year":"2008","unstructured":"Brown, D., Hasler, U., Nunes, P., Bouley, R. & Lu, H. A. Phosphorylation events and the modulation of aquaporin 2 cell surface expression. Curr. Opin. Nephrol. Hypertens. 17, 491\u2013498 (2008).","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"BFncomms13636_CR35","doi-asserted-by":"publisher","first-page":"3882","DOI":"10.1073\/pnas.0910646107","volume":"107","author":"MM Rinschen","year":"2010","unstructured":"Rinschen, M. M. et al. Quantitative phosphoproteomic analysis reveals vasopressin V2-receptor-dependent signaling pathways in renal collecting duct cells. Proc. Natl Acad. Sci. USA 107, 3882\u20133887 (2010).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms13636_CR36","doi-asserted-by":"publisher","first-page":"28980","DOI":"10.1074\/jbc.M702840200","volume":"282","author":"L Ma","year":"2007","unstructured":"Ma, L. & Wang, H. Y. Mitogen-activated protein kinase p38 regulates the Wnt\/cyclic GMP\/Ca2+ non-canonical pathway. J. Biol. Chem. 282, 28980\u201328990 (2007).","journal-title":"J. Biol. Chem."},{"key":"BFncomms13636_CR37","doi-asserted-by":"publisher","first-page":"F473","DOI":"10.1152\/ajprenal.00052.2014","volume":"308","author":"HJ Jung","year":"2015","unstructured":"Jung, H. J. et al. Tankyrase-mediated \u03b2-catenin activity regulates vasopressin-induced AQP2 expression in kidney collecting duct mpkCCDc14 cells. Am. J. Physiol. Renal Physiol. 308, F473\u2013F486 (2015).","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"BFncomms13636_CR38","doi-asserted-by":"publisher","first-page":"9971","DOI":"10.1074\/jbc.M508778200","volume":"281","author":"S Taurin","year":"2006","unstructured":"Taurin, S., Sandbo, N., Qin, Y., Browning, D. & Dulin, N. O. Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase. J. Biol. Chem. 281, 9971\u20139976 (2006).","journal-title":"J. Biol. Chem."},{"key":"BFncomms13636_CR39","doi-asserted-by":"publisher","first-page":"3764","DOI":"10.1091\/mbc.e13-07-0357","volume":"24","author":"H Gon","year":"2013","unstructured":"Gon, H., Fumoto, K., Ku, Y., Matsumoto, S. & Kikuchi, A. Wnt5a signaling promotes apical and basolateral polarization of single epithelial cells. Mol. Biol. Cell 24, 3764\u20133774 (2013).","journal-title":"Mol. Biol. Cell"},{"key":"BFncomms13636_CR40","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1242\/jcs.163683","volume":"128","author":"H Yamamoto","year":"2015","unstructured":"Yamamoto, H. et al. Basolateral secretion of Wnt5a in polarized epithelial cells is required for apical lumen formation. J. Cell Sci. 128, 1051\u20131063 (2015).","journal-title":"J. Cell Sci."},{"key":"BFncomms13636_CR41","doi-asserted-by":"publisher","first-page":"2669","DOI":"10.1681\/ASN.2014111067","volume":"26","author":"JW Lee","year":"2015","unstructured":"Lee, J. W., Chou, C. L. & Knepper, M. A. Deep sequencing in microdissected renal tubules identifies nephron segment-specific transcriptomes. J. Am. Soc. Nephrol. 26, 2669\u20132677 (2015).","journal-title":"J. Am. Soc. Nephrol."},{"key":"BFncomms13636_CR42","doi-asserted-by":"publisher","first-page":"F359","DOI":"10.1152\/ajprenal.00330.2013","volume":"306","author":"CA Miranda","year":"2014","unstructured":"Miranda, C. A., Lee, J. W., Chou, C. L. & Knepper, M. A. Tolvaptan as a tool in renal physiology. Am. J. Physiol. Renal Physiol. 306, F359\u2013F366 (2014).","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"BFncomms13636_CR43","doi-asserted-by":"publisher","first-page":"37821","DOI":"10.1074\/jbc.274.53.37821","volume":"274","author":"U Kessen","year":"1999","unstructured":"Kessen, U., Schaloske, R., Aichem, A. & Mutzel, R. Ca(2+)\/calmodulin-independent activation of calcineurin from Dictyostelium by unsaturated long chain fatty acids. J. Biol. Chem. 274, 37821\u201337826 (1999).","journal-title":"J. Biol. Chem."},{"key":"BFncomms13636_CR44","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1681\/ASN.2012020217","volume":"24","author":"ET Olesen","year":"2013","unstructured":"Olesen, E. T. & Fenton, R. A. Is there a role for PGE2 in urinary concentration? J. Am. Soc. Nephrol. 24, 169\u2013178 (2013).","journal-title":"J. Am. Soc. Nephrol."},{"key":"BFncomms13636_CR45","doi-asserted-by":"publisher","first-page":"F958","DOI":"10.1152\/ajprenal.2001.281.5.F958","volume":"281","author":"I Jo","year":"2001","unstructured":"Jo, I. et al. AQP2 is a substrate for endogenous PP2B activity within an inner medullary AKAP-signaling complex. Am. J. Physiol. Renal Physiol. 281, F958\u2013F965 (2001).","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"BFncomms13636_CR46","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1097\/01.ASN.0000128076.91545.BB","volume":"15","author":"JL Gooch","year":"2004","unstructured":"Gooch, J. L., P\u00e8rgola, P. E., Guler, R. L., Abboud, H. E. & Barnes, J. L. Differential expression of calcineurin A isoforms in the diabetic kidney. J. Am. Soc. Nephrol. 15, 1421\u20131429 (2004).","journal-title":"J. Am. Soc. Nephrol."},{"key":"BFncomms13636_CR47","doi-asserted-by":"publisher","first-page":"2468","DOI":"10.1242\/jcs.02971","volume":"119","author":"JL Gooch","year":"2006","unstructured":"Gooch, J. L., Guler, R. L., Barnes, J. L. & Toro, J. J. Loss of calcineurin Aalpha results in altered trafficking of AQP2 and in nephrogenic diabetes insipidus. J. Cell Sci. 119, 2468\u20132476 (2006).","journal-title":"J. Cell Sci."},{"key":"BFncomms13636_CR48","doi-asserted-by":"publisher","first-page":"3174","DOI":"10.1242\/jcs.150680","volume":"127","author":"HB Moeller","year":"2014","unstructured":"Moeller, H. B., Aroankins, T. S., Slengerik-Hansen, J., Pisitkun, T. & Fenton, R. A. Phosphorylation and ubiquitylation are opposing processes that regulate endocytosis of the water channel aquaporin-2. J. Cell Sci. 127, 3174\u20133183 (2014).","journal-title":"J. Cell Sci."},{"key":"BFncomms13636_CR49","doi-asserted-by":"publisher","first-page":"F233","DOI":"10.1152\/ajprenal.00179.2003","volume":"286","author":"H Lu","year":"2004","unstructured":"Lu, H. et al. Inhibition of endocytosis causes phosphorylation (S256)-independent plasma membrane accumulation of AQP2. Am. J. Physiol. Renal Physiol. 286, F233\u2013F243 (2004).","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"BFncomms13636_CR50","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/S0022-3565(24)36631-5","volume":"281","author":"AJ Rouch","year":"1997","unstructured":"Rouch, A. J., Kudo, L. H. & H\u00e9bert, C. Dexmedetomidine inhibits osmotic water permeability in the rat cortical collecting duct. J. Pharmacol. Exp. Ther. 281, 62\u201369 (1997).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"BFncomms13636_CR51","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1161\/ATVBAHA.107.157438","volume":"28","author":"C Pereira","year":"2008","unstructured":"Pereira, C., Schaer, D. J., Bachli, E. B., Kurrer, M. O. & Schoedon, G. Wnt5A\/CaMKII signaling contributes to the inflammatory response of macrophages and is a target for the antiinflammatory action of activated protein C and interleukin-10. Arterioscler. Thromb. Vasc. Biol. 28, 504\u2013510 (2008).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"BFncomms13636_CR52","doi-asserted-by":"publisher","first-page":"E1407","DOI":"10.1210\/jc.2014-1191","volume":"99","author":"V Catal\u00e1n","year":"2014","unstructured":"Catal\u00e1n, V. et al. Activation of noncanonical Wnt signaling through WNT5A in visceral adipose tissue of obese subjects is related to inflammation. J. Clin. Endocrinol. Metab. 99, E1407\u2013E1417 (2014).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"BFncomms13636_CR53","doi-asserted-by":"publisher","first-page":"550","DOI":"10.2215\/CJN.04071206","volume":"2","author":"IM Wahba","year":"2007","unstructured":"Wahba, I. M. & Mak, R. H. Obesity and obesity-initiated metabolic syndrome: mechanistic links to chronic kidney disease. Clin. J. Am. Soc. Nephrol. 2, 550\u2013562 (2007).","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"BFncomms13636_CR54","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1007\/s00213-002-1130-2","volume":"162","author":"K Tanaka","year":"2002","unstructured":"Tanaka, K. et al. Imipramine, but not lithium, induces the serine\/threonine phosphatase activity of calcineurin without affecting its mRNA expression in the rat brain. Psychopharmacology 162, 339\u2013344 (2002).","journal-title":"Psychopharmacology"},{"key":"BFncomms13636_CR55","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1111\/j.1471-4159.2005.03092.x","volume":"94","author":"WJ Rushlow","year":"2005","unstructured":"Rushlow, W. J., Seah, Y. H., Belliveau, D. J. & Rajakumar, N. Changes in calcineurin expression induced in the rat brain by the administration of antipsychotics. J. Neurochem. 94, 587\u2013596 (2005).","journal-title":"J. Neurochem."},{"key":"BFncomms13636_CR56","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.cmet.2007.03.009","volume":"5","author":"SS Yang","year":"2007","unstructured":"Yang, S. S. et al. Molecular pathogenesis of pseudohypoaldosteronism type II: generation and analysis of a Wnk4(D561A\/+) knockin mouse model. Cell Metab. 5, 331\u2013344 (2007).","journal-title":"Cell Metab."},{"key":"BFncomms13636_CR57","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1042\/BJ20130597","volume":"455","author":"T Mori","year":"2013","unstructured":"Mori, T. et al. Chemical library screening for WNK signalling inhibitors using fluorescence correlation spectroscopy. Biochem. J. 455, 339\u2013345 (2013).","journal-title":"Biochem. J."},{"key":"BFncomms13636_CR58","doi-asserted-by":"publisher","first-page":"C38","DOI":"10.1152\/ajpcell.00109.2012","volume":"304","author":"N Yui","year":"2013","unstructured":"Yui, N. et al. Basolateral targeting and microtubule-dependent transcytosis of the aquaporin-2 water channel. Am. J. Physiol. Cell Physiol. 304, C38\u2013C48 (2013).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"BFncomms13636_CR59","doi-asserted-by":"publisher","first-page":"F317","DOI":"10.1152\/ajprenal.00122.2003","volume":"286","author":"R Quigley","year":"2004","unstructured":"Quigley, R., Chakravarty, S. & Baum, M. Antidiuretic hormone resistance in the neonatal cortical collecting tubule is mediated in part by elevated phosphodiesterase activity. Am. J. Physiol. Renal Physiol. 286, F317\u2013F322 (2004).","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"BFncomms13636_CR60","doi-asserted-by":"publisher","first-page":"9660","DOI":"10.1073\/pnas.95.16.9660","volume":"95","author":"J Schnermann","year":"1998","unstructured":"Schnermann, J. et al. Defective proximal tubular fluid reabsorption in transgenic aquaporin-1 null mice. Proc. Natl Acad. Sci. USA 95, 9660\u20139664 (1998).","journal-title":"Proc. Natl Acad. Sci. USA"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms13636.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms13636","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms13636.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T18:13:36Z","timestamp":1749752016000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms13636"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,28]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFncomms13636"],"URL":"https:\/\/doi.org\/10.1038\/ncomms13636","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.727038153.793555516","asserted-by":"object"}]},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,28]]},"assertion":[{"value":"22 August 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 October 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"13636"}}