title: Regulation of the assembly and adhesion activity of E-cadherin by nectin and afadin for the formation of adherens junctions in Madin-Darby canine kidney cells.
abstract: The Ca2+-independent immunoglobulin-like molecule nectin first forms cell-cell adhesion and then assembles cadherin at nectin-based cell-cell adhesion sites, resulting in the formation of adherens junctions (AJs). Afadin is a nectin- and actin filament-binding protein that connects nectin to the actin cytoskeleton. Here, we studied the roles and modes of action of nectin and afadin in the formation of AJs in cultured MDCK cells. The trans-interaction of nectin assembled E-cadherin, which associated with p120(ctn), beta-catenin, and alpha-catenin, at the nectin-based cell-cell adhesion sites in an afadin-independent manner. However, the assembled E-cadherin showed weak cell-cell adhesion activity and might be the non-trans-interacting form. This assembly was mediated by the IQGAP1-dependent actin cytoskeleton, which was organized by Cdc42 and Rac small G proteins that were activated by the action of trans-interacting nectin through c-Src and Rap1 small G protein in an afadin-independent manner. However, Rap1 bound to afadin, and this Rap1-afadin complex then interacted with p120(ctn) associated with non-trans-interacting E-cadherin, thereby causing the trans-interaction of E-cadherin. Thus, nectin regulates the assembly and cell-cell adhesion activity of E-cadherin through afadin, nectin signaling, and p120(ctn) for the formation of AJs in Madin-Darby canine kidney cells.
authors.affiliation: Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Sato
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Fujita
authors.forename: Akio
authors.initials: A
authors.lastname: Yamada
authors.forename: Takako
authors.initials: T
authors.lastname: Ooshio
authors.forename: Ryoko
authors.initials: R
authors.lastname: Okamoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Irie
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism; D022005:Adherens Junctions; D000818:Animals; D019921:Biotinylation; D015820:Cadherins / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D051177:Catenins; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002450:Cell Communication; D002460:Cell Line; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism; D004285:Dogs; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D047468:Immunoprecipitation; D007668:Kidney / Q000378:metabolism*; D008840:Microfilament Proteins / Q000737:chemistry / Q000502:physiology*; D008856:Microscopy, Fluorescence; D000075983:Nectins; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D015398:Signal Transduction; D051178:alpha Catenin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000378:metabolism; D000095002:Delta Catenin
chemical_list: D000199:Actins; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; C101203:IQ motif containing GTPase activating protein 1; D008840:Microfilament Proteins; D000075983:Nectins; D010750:Phosphoproteins; C108835:afadin; D051178:alpha Catenin; D051176:beta Catenin; D020703:ras GTPase-Activating Proteins; D049452:Green Fluorescent Proteins; D002118:Calcium; D000095002:Delta Catenin