Epithelial cells are associated laterally in a sheet, with the apical surface facing the lumina, often covered by microvilli, and the basolateral side underlying connective tissue. Development and maintenance of epithelial polarity require cell–substrate and cell–cell adhesions that promote localized assembly of submembranous cytoskeleton networks and specialized membrane intracellular transport pathways. The assembly of tight junctions (TJs) plays a key role in the formation of structurally and functionally distinct basolateral and apical plasma membrane (PM) domains. How are the PM proteins delivered to specialized and polarized cell surface domains? Even though the involvement of v- and t-soluble N-ethylmaleimide–sensitive factor attachment protein receptors (SNAREs) in apical and basolateral PM delivery is now well established, are these proteins sufficient to specify vesicle docking and fusion at sites in the appropriate membrane domains? Recent data highlight TJs as major sites for...

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