{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:40:00Z","timestamp":1791322800785,"version":"4.3.1"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:p>\n                    ATPase H\n                    <jats:sup>+<\/jats:sup>\n                    -transporting lysosomal accessory protein 2 (Atp6ap2), also known as the (pro)renin receptor, is a type 1 transmembrane protein and an accessory subunit of the vacuolar H\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase (V-ATPase) that may also function within the renin-angiotensin system. However, the contribution of Atp6ap2 to renin-angiotensin-dependent functions remains unconfirmed. Using mice with an inducible conditional deletion of Atp6ap2 in mouse renal epithelial cells, we found that decreased V-ATPase expression and activity in the intercalated cells of the collecting duct impaired acid-base regulation by the kidney. In addition, these mice suffered from marked polyuria resistant to desmopressin administration. Immunoblotting revealed downregulation of the medullary Na\n                    <jats:sup>+<\/jats:sup>\n                    -K\n                    <jats:sup>+<\/jats:sup>\n                    -2Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    cotransporter NKCC2 in these mice compared with wild-type mice, an effect accompanied by a hypotonic medullary interstitium and impaired countercurrent multiplication. This phenotype correlated with strong autophagic defects in epithelial cells of medullary tubules. Notably, cells with high accumulation of the autophagosomal substrate p62 displayed the strongest reduction of NKCC2 expression. Finally, nephron-specific Atp6ap2 depletion did not affect angiotensin II production, angiotensin II-dependent BP regulation, or sodium handling in the kidney. Taken together, our results show that nephron-specific deletion of Atp6ap2 does not affect the renin-angiotensin system but causes a combination of renal concentration defects and distal renal tubular acidosis as a result of impaired V-ATPase activity.\n                  <\/jats:p>","DOI":"10.1681\/asn.2015080915","type":"journal-article","created":{"date-parts":[[2016,4,4]],"date-time":"2016-04-04T22:53:51Z","timestamp":1459810431000},"page":"3320-3330","source":"Crossref","is-referenced-by-count":89,"title":["Renal Atp6ap2\/(Pro)renin Receptor Is Required for Normal Vacuolar H+-ATPase Function but Not for the Renin-Angiotensin System"],"prefix":"10.1681","volume":"27","author":[{"given":"Francesco","family":"Trepiccione","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 Mixte de Recherche_S970, Paris Centre de Recherche Cardiovasculaire, H\u00f4pital Europ\u00e9en Georges Pompidou, Assistance Publique H\u00f4pitaux de Paris, Paris, France;"},{"name":"Department of Cardio-Thoracic and Respiratory Science, Second University of Naples, Caserta, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon D.","family":"Gerber","sequence":"additional","affiliation":[{"name":"Imagine Institute, Paris Descartes University\u2013Sorbonne Paris Cit\u00e9, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Grahammer","sequence":"additional","affiliation":[{"name":"Renal Division, University Medical Center Freiburg, Freiburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen I.","family":"L\u00f3pez-Cayuqueo","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 Mixte de Recherche_S970, Paris Centre de Recherche Cardiovasculaire, H\u00f4pital Europ\u00e9en Georges Pompidou, Assistance Publique H\u00f4pitaux de Paris, Paris, France;"},{"name":"Centro de Estudios Cient\u00edficos, Valdivia, Chile;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Baudrie","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 Mixte de Recherche_S970, Paris Centre de Recherche Cardiovasculaire, H\u00f4pital Europ\u00e9en Georges Pompidou, Assistance Publique H\u00f4pitaux de Paris, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodor G.","family":"P\u0103unescu","sequence":"additional","affiliation":[{"name":"Program in Membrane Biology\/Nephrology Division, Massachusetts General Hospital\/Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane E.","family":"Capen","sequence":"additional","affiliation":[{"name":"Program in Membrane Biology\/Nephrology Division, Massachusetts General Hospital\/Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Picard","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique Equipe de Recherche Labelis\u00e9e 8228, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 Mixte de Recherche_S1138, Centre de Recherche des Cordeliers, Universit\u00e9 Pierre et Marie Curie, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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