Abstract
Tight junctions (TJs) and adherens junctions (AJs) regulate epithelial differentiation and functions. The exocytic delivery to the cell surface is crucial for TJ/AJ assembly, however, little is known about the mechanisms of junctional exocytosis. The aim of this study was to investigate whether a key exocytosis molecule, soluble N-ethylmaleimide sensitive factor (NSF) attachment protein alpha (α-SNAP), regulates epithelial junctions. α-SNAP was enriched at TJs and AJs in cultured colonic epithelial cells and in human intestinal mucosa. Small interfering RNA-mediated knockdown of α-SNAP in SK-CO15 cells exerted two independent effects. First, α-SNAP-depleted cells failed to assemble AJs and TJs and establish the paracellular barrier. Such junctional disruption was accompanied by down-regulation of p120 catenin and p120 catenin depletion phenocopied effects of α-SNAP knockdown on AJ/TJ structure and functions. Second, α-SNAP depletion induced apoptosis. Such apoptosis was accompanied by down-regulation of Bcl-2 protein; it was mimicked by inhibition, and prevented by overexpression of Bcl-2. AJ/TJ disassembly and apoptosis in α-SNAP-depleted cells were NSF-independent and appeared to be linked to Golgi fragmentation. These findings suggest novel roles for α-SNAP in regulating cell-cell adhesion and survival in human epithelia. Supported by NIH grants DK083968 and DK084953 to AII.
Published Version
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