Nectin and junctional adhesion molecule are critical cell adhesion molecules for the apico-basal alignment of adherens and tight junctions in epithelial cells

Authors

  • Tomohiro Yamada,

    1. KAN Research Institute, Inc., Chuo-ku, Kobe, Japan
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  • Kaori Kuramitsu,

    1. Department of Molecular Biology and Biochemistry, Faculty of Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
    Current affiliation:
    1. Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan
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  • Etsuko Rikitsu,

    1. KAN Research Institute, Inc., Chuo-ku, Kobe, Japan
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  • Souichi Kurita,

    1. Division of Molecular and Cellular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan
    2. Division of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan
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  • Wataru Ikeda,

    1. KAN Research Institute, Inc., Chuo-ku, Kobe, Japan
    2. Department of Molecular Biology and Biochemistry, Faculty of Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
    3. Division of Molecular and Cellular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan
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  • Yoshimi Takai

    Corresponding author
    1. Department of Molecular Biology and Biochemistry, Faculty of Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
    2. Division of Molecular and Cellular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan
    3. Division of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan
    4. CREST, JST, Chuo-ku, Kobe, Japan
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Abstract

Tight junctions (TJs) and adherens junctions (AJs) form an apical junctional complex at the apical side of the lateral membranes of epithelial cells, in which TJs are aligned at the apical side of AJs. Many cell adhesion molecules (CAMs) and cell polarity molecules (CPMs) cooperatively regulate the formation of the apical junctional complex, but the mechanism for the alignment of TJs at the apical side of AJs is not fully understood. We developed a cellular system with which epithelial-like TJs and AJs were reconstituted in fibroblasts and analyzed the cooperative roles of CAMs and CPMs. We exogenously expressed various combinations of CAMs and CPMs in fibroblasts that express negligible amounts of these molecules endogenously. In these cells, the nectin-based cell–cell adhesion was formed at the apical side of the junctional adhesion molecule (JAM)-based cell–cell adhesion, and cadherin and claudin were recruited to the nectin-3- and JAM-based cell–cell adhesion sites to form AJ-like and TJ-like domains, respectively. This inversed alignment of the AJ-like and TJ-like domains was reversed by complementary expression of CPMs Par-3, atypical protein kinase C, Par-6, Crb3, Pals1 and Patj. We describe the cooperative roles of these CAMs and CPMs in the apico-basal alignment of TJs and AJs in epithelial cells.

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