The WD40 protein Morg1 facilitates Par6-aPKC binding to Crb3 for apical identity in epithelial cells.

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, COS Cells, Cell Line, Tumor, Cell Membrane, Cell Polarity, Cercopithecus aethiops, Dogs, Epithelial Cells, Kidney, Madin Darby Canine Kidney Cells, Membrane Glycoproteins, Morphogenesis, Mutagenesis, Site-Directed, Mutation, Protein Binding, Protein Kinase C, Protein Transport, RNA Interference, Tight Junctions, Time Factors, Transfection, cdc42 GTP-Binding Protein
J. Cell Biol.
Date: Mar. 04, 2013
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