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Inactivation of some of the polarity complexes results in cystic kidneys, and apical\u2010basolateral polarity defects are commonly observed in autosomal\u2010dominant polycystic kidney disease (ADPKD); however, little is known about the role that polarity complexes play in ADPKD. Here, we demonstrate that Scribble, a core protein of the SCRIB complex, is down\u2010regulated in ADPKD cell lines and the zebrafish model of this disease\n                    <jats:italic>(pkd2<\/jats:italic>\n                    mor\u2010phants). Overexpression of Scribble could reduce cyst formation in\n                    <jats:italic>pkd2<\/jats:italic>\n                    morphants, and loss of\n                    <jats:italic>scrib<\/jats:italic>\n                    led to a dilated pronephric duct in zebrafish. Furthermore, the Hippo signaling pathway was inactivated in\n                    <jats:italic>scrib<\/jats:italic>\n                    mutants and\n                    <jats:italic>pkd2<\/jats:italic>\n                    morphants in which Yes\u2010associated protein (YAP), which is physiologically locatedinthe cytoplasm, was translocated to the nucleus. Of note, overexpression of cytoplasmic YAP, instead of nuclear YAP, could reduce cyst formation in\n                    <jats:italic>pkd2<\/jats:italic>\n                    morphants. Consistently, knockout of\n                    <jats:italic>yap<\/jats:italic>\n                    resulted in cystic kidneys in zebrafish, which was rescued by the overexpression of cytoplasmic YAP, but not nuclear YAP. Finally,\n                    <jats:italic>scrib<\/jats:italic>\n                    and\n                    <jats:italic>yap<\/jats:italic>\n                    had a genetic interaction with\n                    <jats:italic>pkd2<\/jats:italic>\n                    in cyst formation, and the overexpression of Scribble attenuated the down\u2010regulation of cytoplasmic YAP in ADPKD. Altogether, our data indicate that Scribble induces the phosphorylation of YAP and, consequently, influences cyst formation in ADPKD by mediating YAP nucleocytoplasmic shuttling.\u2014Xu, D., Lv, J., He, L., Fu, L., Hu, R., Cao, Y., Mei, C. Scribble influences cyst formation in autosomal\u2010dominant polycystic kidney disease by regulating Hippo signaling pathway.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 32, 4394\u20134407 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201701376rr","type":"journal-article","created":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T18:16:27Z","timestamp":1520878587000},"page":"4394-4407","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Scribble influences cyst formation in autosomal\u2010dominant polycystic kidney disease by regulating Hippo signaling pathway"],"prefix":"10.1096","volume":"32","author":[{"given":"Dechao","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Nephrology Kidney 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