{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T23:11:54Z","timestamp":1791155514984,"version":"4.1.0"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,1]]},"abstract":"\n Phosphoinositides, a family of phosphorylated derivatives of phosphatidylinositol (PtdIns), are tightly regulated both temporally and spatially by PtdIns phosphatases and kinases. Mutations in\n inositol polyphosphate 5-phosphatase E<\/jats:italic>\n (\n INPP5E<\/jats:italic>\n ) cause Joubert syndrome, a human disorder associated with numerous ciliopathic defects, including renal cyst formation, linking phosphoinositides to ciliopathies. However, the molecular mechanism by which INPP5E-mediated PtdIns signaling regulates ciliogenesis and cystogenesis is unclear. Here, we utilized an\n in vivo<\/jats:italic>\n vertebrate model of renal cystogenesis to show that Inpp5e enzymatic activity at the apical membrane directs apical docking of basal bodies in renal epithelia. Knockdown or knockout of\n inpp5e<\/jats:italic>\n led to ciliogenesis defects and cystic kidneys in zebrafish. Furthermore, knockdown of\n inpp5e<\/jats:italic>\n in embryos led to defects in cell polarity, cortical organization of F-actin, and apical segregation of PtdIns(4,5)P\n 2<\/jats:sub>\n and PtdIns(3,4,5)P\n 3<\/jats:sub>\n . Knockdown of the\n ezrin<\/jats:italic>\n gene, which encodes an ezrin\/radixin\/moesin (ERM) protein that crosslinks PtdIns(4,5)P\n 2<\/jats:sub>\n and F-actin, phenocopied\n inpp5e<\/jats:italic>\n knockdowns. Notably, overexpression of the\n ezrin<\/jats:italic>\n gene rescued\n inpp5e<\/jats:italic>\n morphants. Finally, treatment with the PI 3-kinase inhibitor LY294002, which decreases PtdIns(3,4,5)P\n 3<\/jats:sub>\n levels, rescued the cellular, phenotypic, and renal functional defects in\n inpp5e<\/jats:italic>\n -knockdown embryos. Together, our data indicate that Inpp5e functions as a key regulator of cell polarity in the renal epithelia, by inhibiting PtdIns(3,4,5)P\n 3<\/jats:sub>\n and subsequently stabilizing PtdIns(4,5)P\n 2<\/jats:sub>\n and recruiting Ezrin, F-actin, and basal bodies to the apical membrane, and suggest a possible novel approach for treating human ciliopathies.\n <\/jats:p>","DOI":"10.1681\/asn.2015080906","type":"journal-article","created":{"date-parts":[[2016,7,12]],"date-time":"2016-07-12T01:54:29Z","timestamp":1468288469000},"page":"118-129","source":"Crossref","is-referenced-by-count":49,"title":["The Joubert Syndrome Protein Inpp5e Controls Ciliogenesis by Regulating Phosphoinositides at the Apical Membrane"],"prefix":"10.1681","volume":"28","author":[{"given":"Wenyan","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Molecular and Cell Biology, Tongji University School of Life Sciences and Technology, Shanghai, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Tongji University School of Life Sciences and Technology, Shanghai, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruikun","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Tongji University School of Life Sciences and Technology, Shanghai, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Tongji University School of Life Sciences and Technology, Shanghai, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Tongji University School of Life Sciences and Technology, Shanghai, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiaulou","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Tongji University School of Life Sciences and Technology, Shanghai, China;"},{"name":"Tongji University and Shanghai Changzheng Hospital Joint Research Center for Translational Medicine, Changzheng Hospital, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,7,8]]},"reference":[{"key":"B1-20230819","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nrg2774","article-title":"The primary cilium: a signalling centre during vertebrate 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