The cerebral cavernous malformation disease causing gene KRIT1 participates in intestinal epithelial barrier maintenance and regulation

Epithelial barrier maintenance and regulation requires an intact perijunctional actomyosin ring underneath the cell–cell junctions. By searching for known factors affecting the actin cytoskeleton, we identified Krev interaction trapped protein 1 (KRIT1) as a major regulator for epithelial barrier function through multiple mechanisms. KRIT1 is expressed in both small intestinal and colonic epithelium, and KRIT1 knockdown in differentiated Caco-2 intestinal epithelium decreases epithelial barrier function and increases cation selectivity. KRIT1 knockdown abolished Rho-associated protein kinase–induced and myosin II motor inhibitor–induced barrier loss by limiting both small and large molecule permeability but did not affect myosin light chain kinase–induced increases in epithelial barrier function. These data suggest that KRIT1 participates in Rho-associated protein kinase– and myosin II motor–dependent (but not myosin light chain kinase–dependent) epithelial barrier regulation. KRIT1 knockdown exacerbated ...