title: Role of nectin in formation of E-cadherin-based adherens junctions in keratinocytes: analysis with the N-cadherin dominant negative mutant.
abstract: E-cadherin is a Ca(2+)-dependent cell-cell adhesion molecule at adherens junctions (AJs) of epithelial cells. A fragment of N-cadherin lacking its extracellular region serves as a dominant negative mutant (DN) and inhibits cell-cell adhesion activity of E-cadherin, but its mode of action remains to be elucidated. Nectin is a Ca(2+)-independent immunoglobulin-like cell-cell adhesion molecule at AJs and is associated with E-cadherin through their respective peripheral membrane proteins, afadin and catenins, which connect nectin and cadherin to the actin cytoskeleton, respectively. We showed here that overexpression of nectin capable of binding afadin, but not a mutant incapable of binding afadin, reduced the inhibitory effect of N-cadherin DN on the cell-cell adhesion activity of E-cadherin in keratinocytes. Overexpressed nectin recruited N-cadherin DN to the nectin-based cell-cell adhesion sites in an afadin-dependent manner. Moreover, overexpression of nectin enhanced the E-cadherin-based cell-cell adhesion activity. These results suggest that N-cadherin DN competitively inhibits the association of the endogenous nectin-afadin system with the endogenous E-cadherin-catenin system and thereby reduces the cell-cell adhesion activity of E-cadherin. Thus, nectin plays a role in the formation of E-cadherin-based AJs in keratinocytes.
authors.affiliation: Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kakunaga
authors.forename: Noriko
authors.initials: N
authors.lastname: Okabe
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kawakatsu
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimizu
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D015820:Cadherins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015870:Gene Expression; D015603:Keratinocytes / Q000378:metabolism*; D016547:Kinesins; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D009154:Mutation; D009218:Myosins; D000075983:Nectins; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: C490657:Afdn protein, mouse; D015820:Cadherins; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D000075983:Nectins; D010446:Peptide Fragments; C108835:afadin; D009218:Myosins; D016547:Kinesins