title: The WD40 protein Morg1 facilitates Par6-aPKC binding to Crb3 for apical identity in epithelial cells.
abstract: Formation of apico-basal polarity in epithelial cells is crucial for both morphogenesis (e.g., cyst formation) and function (e.g., tight junction development). Atypical protein kinase C (aPKC), complexed with Par6, is considered to translocate to the apical membrane and function in epithelial cell polarization. However, the mechanism for translocation of the Par6-aPKC complex has remained largely unknown. Here, we show that the WD40 protein Morg1 (mitogen-activated protein kinase organizer 1) directly binds to Par6 and thus facilitates apical targeting of Par6-aPKC in Madin-Darby canine kidney epithelial cells. Morg1 also interacts with the apical transmembrane protein Crumbs3 to promote Par6-aPKC binding to Crumbs3, which is reinforced with the apically localized small GTPase Cdc42. Depletion of Morg1 disrupted both tight junction development in monolayer culture and cyst formation in three-dimensional culture; apico-basal polarity was notably restored by forced targeting of aPKC to the apical surface. Thus, Par6-aPKC recruitment to the premature apical membrane appears to be required for definition of apical identity of epithelial cells.
authors: Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors: Junya
authors: J
authors: Hayase
authors: Sachiko
authors: S
authors: Kamakura
authors: Yuko
authors: Y
authors: Iwakiri
authors: Yoshihiro
authors: Y
authors: Yamaguchi
authors: Tomoko
authors: T
authors: Izaki
authors: Takashi
authors: T
authors: Ito
authors: Hideki
authors: H
authors: Sumimoto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000201:enzymology*; D016764:Cell Polarity; D002522:Chlorocebus aethiops; D004285:Dogs; D004847:Epithelial Cells / Q000201:enzymology*; D007668:Kidney / Q000196:embryology / Q000201:enzymology*; D061985:Madin Darby Canine Kidney Cells; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009024:Morphogenesis; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011485:Protein Binding; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D034622:RNA Interference; D019108:Tight Junctions / Q000201:enzymology; D013997:Time Factors; D014162:Transfection; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C472002:CRB3 protein, human; D008562:Membrane Glycoproteins; C499657:PARD6A protein, human; C542372:WDR83 protein, human; C115015:PKC-3 protein; D011493:Protein Kinase C; D020764:cdc42 GTP-Binding Protein