Zusammenfassung
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 threedimensional matrix indicating the requirement of JAM-A for the development of apico-basal
polarity. To define the regions of ...
Zusammenfassung
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 threedimensional 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 domainbinding 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 apicobasal polarity in epithelial cells and identify regions in JAM-A which are critical for this role.
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