Myosin light chain kinase: pulling the strings of epithelial tight junction function

Dynamic regulation of paracellular permeability is essential for physiological epithelial function, while dysregulated permeability is commonindisease. The recent elucidationof themolecular compositionof the epithelial tight junction complex has been accompanied by characterization of diverse intracellular mediators of paracellular permeabiltiy. Myosin light chain kinase (MLCK), which induces contraction of the perijunctional actomyosin ring throughmyosin II regulatory light chain phosphorylation, has emerged as a key regulator of tight junction permeability. Examination of the regulation and role of MLCK in tight junction dysfunction has helped to define pathological processes and characterize the role of barrier loss in disease pathogenesis, and may provide future therapeutic targets to treat intestinal disease.