No Static at All A New Perspective on Molecular Architecture of the Tight Junction

Permeability of the intestinal epithelial barrier is regulated in response to physiological and pathophysiological stimuli. Recent work has characterized a critical role of acute tight junction regulation in diarrhea secondary to T cell activation and cytokine release. The intracellular mediators of the ensuing barrier dysfunction include myosin light chain kinase, which phosphorylates myosin II regulatory light chain and triggers structural tight junction reorganization. While the molecular intermediates in this reorganization are not defined, the new discovery that individual tight junction-associated proteins are highly dynamic at steady state may provide insight into the mechanisms of regulation.