Abstract
Pathogens and other external stressors disrupt integrity of epithelial barriers by disassembling tight junctions (TJ) and adherens junctions (AJ), however the role of stress‐related signaling in junctional disassembly remains poorly understood. The aim of this study was to investigate the role of a stress‐activated c‐Jun N‐terminal kinase (JNK) in disruption of apical junctions in model intestinal epithelia. A rapid AJ/TJ disassembly triggered by extracellular calcium depletion in T84 and SK‐CO15 cell monolayers was accompanied by activation (phosphorylation) of JNK and prevented by different pharmacological inhibitors of JNK. JNK‐1 but not JNK‐2 colocalized with mature apical junctions and siRNA‐mediated down‐regulation of JNK‐1 attenuated disruption of AJ and TJ in calcium‐depleted SK‐CO15 cells. Correspondingly, reassembly of apical junctions was accelerated by a JNK inhibitor, SP600125, and suppressed by JNK activator, anisomycin. In calcium‐depleted epithelial cells, inhibition of JNK blocked formation of contractile F‐actin rings suggesting that JNK regulates junctions by reorganizing the actin cytoskeleton. Furthermore, pharmacological analysis has shown that JNK signals downstream of Rho‐dependent kinase (ROCK). These finding suggest a novel role for JNK in the signaling pathway that links ROCK and F‐actin remodeling and leads to disassembly of epithelial apical junctions.
Published Version
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