title: Junctional adhesion molecule-a participates in the formation of apico-basal polarity through different domains.
abstract: Junctional adhesion molecule (JAM)-A is an integral membrane protein at tight junctions of epithelial cells which associates with the cell polarity protein PAR-3. Here, we demonstrate that downregulation of JAM-A impairs the ability of MDCK II cells to form cysts in a three-dimensional matrix indicating the requirement of JAM-A for the development of apico-basal polarity. To define the regions of JAM-A important for this function, we have generated MDCK II cell lines stably expressing inducible JAM-A mutants. Mutants of JAM-A which were designed to mislocalize strongly impaired the development of cysts and the formation of functional tight junctions. Surprisingly, similar mutants that lacked the PDZ domain-binding motif at the C-terminus were still impaired in apico-basal polarity formation suggesting that additional regions within the cytoplasmic tail of JAM-A are important for the function of JAM-A. A JAM-A mutant lacking the first Ig-like domain necessary for homophilic binding localized to cell-cell contacts similar to wild-type JAM-A. However, despite this same localization, this mutant interfered with cell polarity and tight junction formation. Together our findings suggest an important role for JAM-A in the development of apico-basal polarity in epithelial cells and identify regions in JAM-A which are critical for this role.
authors.affiliation: Institute of Cell Biology, ZMBE, University of Münster, D-48149 Münster, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rehder
authors.forename: Sandra
authors.initials: S
authors.lastname: Iden
authors.forename: Ines
authors.initials: I
authors.lastname: Nasdala
authors.forename: Joachim
authors.initials: J
authors.lastname: Wegener
authors.forename: Maria-Katharina Meyer Zu
authors.initials: MK
authors.lastname: Brickwedde
authors.forename: Dietmar
authors.initials: D
authors.lastname: Vestweber
authors.forename: Klaus
authors.initials: K
authors.lastname: Ebnet
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology*; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology; D062726:Junctional Adhesion Molecules; D017434:Protein Structure, Tertiary; D019108:Tight Junctions / Q000502:physiology
chemical_list: D015815:Cell Adhesion Molecules; D062726:Junctional Adhesion Molecules