{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:47:06Z","timestamp":1787017626484,"version":"build-2736575974"},"reference-count":49,"publisher":"American Physiological Society","issue":"6","funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","doi-asserted-by":"publisher","award":["R21 DK092619"],"award-info":[{"award-number":["R21 DK092619"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","doi-asserted-by":"publisher","award":["R01 DK38452 and R01 DK096586"],"award-info":[{"award-number":["R01 DK38452 and R01 DK096586"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"crossref","award":["BES 2011-045069"],"award-info":[{"award-number":["BES 2011-045069"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"crossref","award":["SAF 2010-16198"],"award-info":[{"award-number":["SAF 2010-16198"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2016,12,1]]},"abstract":"<jats:p>Within the past decade tremendous efforts have been made to understand the mechanism behind aquaporin-2 (AQP2) water channel trafficking and recycling, to open a path toward effective diabetes insipidus therapeutics. A recent study has shown that integrin-linked kinase (ILK) conditional-knockdown mice developed polyuria along with decreased AQP2 expression. To understand whether ILK also regulates AQP2 trafficking in kidney tubular cells, we performed in vitro analysis using LLCPK1 cells stably expressing rat AQP2 (LLC-AQP2 cells). Upon treatment of LLC-AQP2 cells with ILK inhibitor cpd22 and ILK-siRNA, we observed increased accumulation of AQP2 in the perinuclear region, without any significant increase in the rate of endocytosis. This perinuclear accumulation did not occur in cells expressing a serine-256-aspartic acid mutation that retains AQP2 in the plasma membrane. We then examined clathrin-mediated endocytosis after ILK inhibition using rhodamine-conjugated transferrin. Despite no differences in overall transferrin endocytosis, the endocytosed transferrin also accumulated in the perinuclear region where it colocalized with AQP2. These accumulated vesicles also contained the recycling endosome marker Rab11. In parallel, the usual vasopressin-induced AQP2 membrane accumulation was prevented after ILK inhibition; however, ILK inhibition did not measurably affect AQP2 phosphorylation at serine-256 or its dephosphorylation at serine-261. Instead, we found that inhibition of ILK increased F-actin polymerization. When F-actin was depolymerized with latrunculin, the perinuclear located AQP2 dispersed. We conclude that ILK is important in orchestrating dynamic cytoskeletal architecture during recycling of AQP2, which is necessary for its subsequent entry into the exocytotic pathway.<\/jats:p>","DOI":"10.1152\/ajprenal.00336.2016","type":"journal-article","created":{"date-parts":[[2016,10,19]],"date-time":"2016-10-19T21:43:46Z","timestamp":1476913426000},"page":"F1346-F1357","source":"Crossref","is-referenced-by-count":18,"title":["ILK and cytoskeletal architecture: an important determinant of AQP2 recycling and subsequent entry into the exocytotic pathway"],"prefix":"10.1152","volume":"311","author":[{"given":"Fahmy A.","family":"Mamuya","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Luis","family":"Cano-Pe\u00f1alver","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Physiology Unit, Universidad de Alcal\u00e1, Alcal\u00e1 de Henares, Madrid, Spain; Instituto Reina Sofia de Investigaci\u00f3n Renal and Red de Investigaci\u00f3n Renal (REDinREN), Instituto de Salud Carlos III, Madrid, Spain; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Rodriguez Puyol","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation and Nephrology Department, Hospital Pr\u00edncipe de Asturias, Alcal\u00e1 de Henares, and Instituto Reina Sofia de Investigaci\u00f3n Renal and REDinREN from Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Rodriguez Puyol","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Physiology Unit, Universidad de Alcal\u00e1, Alcal\u00e1 de Henares, Madrid, Spain; Instituto Reina Sofia de Investigaci\u00f3n Renal and Red de Investigaci\u00f3n Renal (REDinREN), Instituto de Salud Carlos III, Madrid, Spain; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"de Frutos","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Physiology Unit, Universidad de Alcal\u00e1, Alcal\u00e1 de Henares, Madrid, Spain; Instituto Reina Sofia de Investigaci\u00f3n Renal and Red de Investigaci\u00f3n Renal (REDinREN), Instituto de Salud Carlos III, Madrid, Spain; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua Ann Jenny","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00152.2015"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9594"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2005.09.002"},{"key":"B4","first-page":"p. 302","volume-title":"Brenner and Rector\u2019s The Kidney","author":"Brown D","year":"2015"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-249250"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012010079"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1991.260.1.C9"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208427"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712338105"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nature08908"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/379091a0"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/BF00852577"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00284.2006"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.1985.Supplement_3.17"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.5049\/EBP.2010.8.2.59"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1997.272.6.F816"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.16.7212"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00519.2010"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010270200"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2013.12.002"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1021\/jm2007744"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00001.2011"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1309219110"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00179.2003"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00072.2008"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1242\/dev.091298"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5869"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.505"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2006.00508.x"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00291.2004"},{"key":"B31","first-page":"136","volume":"15","author":"Nielsen S","year":"2000","journal-title":"News Physiol Sci"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00344.2008"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.5049\/EBP.2015.13.1.1"},{"key":"B34","first-page":"1337","volume":"20","author":"Peroukides S","year":"2008","journal-title":"Oncol Rep"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.7.3207"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90339.2008"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0131719"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032843"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00437.2005"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00257.2001"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-008-0457-0"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02495"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0868"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1007\/BF00860757"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-012-2118-8"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.09.007"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-013-0789-5"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200108077"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1242\/bio.2011042"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00336.2016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T17:23:48Z","timestamp":1567963428000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00336.2016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,1]]},"references-count":49,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016,12,1]]}},"alternative-id":["10.1152\/ajprenal.00336.2016"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00336.2016","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,1]]}}}