title: Two cell adhesion molecules, nectin and cadherin, interact through their cytoplasmic domain-associated proteins.
abstract: We have found a new cell-cell adhesion system at cadherin-based cell-cell adherens junctions (AJs) consisting of at least nectin and l-afadin. Nectin is a Ca(2+)-independent homophilic immunoglobulin-like adhesion molecule, and l-afadin is an actin filament-binding protein that connects the cytoplasmic region of nectin to the actin cytoskeleton. Both the trans-interaction of nectin and the interaction of nectin with l-afadin are necessary for their colocalization with E-cadherin and catenins at AJs. Here, we examined the mechanism of interaction between these two cell-cell adhesion systems at AJs by the use of alpha-catenin-deficient F9 cell lines and cadherin-deficient L cell lines stably expressing their various components. We showed here that nectin and E-cadherin were colocalized through l-afadin and the COOH-terminal half of alpha-catenin at AJs. Nectin trans-interacted independently of E-cadherin, and the complex of E-cadherin and alpha- and beta-catenins was recruited to nectin-based cell-cell adhesion sites through l-afadin without the trans-interaction of E-cadherin. Our results indicate that nectin and cadherin interact through their cytoplasmic domain-associated proteins and suggest that these two cell-cell adhesion systems cooperatively organize cell-cell AJs.
authors.affiliation: Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tachibana
authors.forename: H
authors.initials: H
authors.lastname: Nakanishi
authors.forename: K
authors.initials: K
authors.lastname: Mandai
authors.forename: K
authors.initials: K
authors.lastname: Ozaki
authors.forename: W
authors.initials: W
authors.lastname: Ikeda
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: A
authors.initials: A
authors.lastname: Nagafuchi
authors.forename: S
authors.initials: S
authors.lastname: Tsukita
authors.forename: Y
authors.initials: Y
authors.lastname: Takai
mesh_terms: D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D015820:Cadherins / Q000737:chemistry* / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D018920:Coculture Techniques; D003593:Cytoplasm / Q000502:physiology / Q000648:ultrastructure; D003598:Cytoskeletal Proteins / Q000502:physiology; D018076:DNA, Complementary; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology* / Q000648:ultrastructure; D016547:Kinesins; D007739:L Cells; D051379:Mice; D008840:Microfilament Proteins / Q000502:physiology; D008969:Molecular Sequence Data; D009218:Myosins; D000075983:Nectins; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014162:Transfection; D051178:alpha Catenin
chemical_list: C095516:AFDN protein, human; C490657:Afdn protein, mouse; C495273:CTNNA1 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; C495272:Ctnna1 protein, mouse; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D008840:Microfilament Proteins; D000075983:Nectins; D011991:Receptors, Virus; D011994:Recombinant Proteins; C108835:afadin; D051178:alpha Catenin; D009218:Myosins; D016547:Kinesins