Skip to main content
. 2018 Jan;10(1):a029314. doi: 10.1101/cshperspect.a029314

Figure 3.

Figure 3.

Tight junction flux pathways in disease. Transgenic, intestinal epithelial-restricted expression of constitutively active-MLCK restores sensitivity of long MLCK−/− mice to CD4+CD45RBhi-adoptive transfer colitis, an immune-mediated experimental inflammatory bowel disease (IBD). (A) Long myosin light chain kinase (MLCK) is essential for myosin II regulatory light chain (MLC) phosphorylation and claudin-2 upregulation during immune-mediated experimental IBD. Long MLCK−/− mice are protected from disease-associated MLC phosphorylation and claudin-2 upregulation. Tissue specific, intestinal epithelial expression of a constitutively active MLCK catalytic domain (CA-MLCK) restores disease-associated MLC phosphorylation and claudin-2 upregulation. Serine-19-phosphorylated MLC (phosphoMLC) or claudin-2 (green) and nuclei (blue) are shown. Bar = 10 um. (B) Diagram of intestinal permeability pathways in disease. Pore and leak pathways are regulated by claudin-2 expression and MLCK-dependent occludin endocytosis, respectively. The unrestricted pathway is a tight junction-independent pathway at sites of epithelial damage (e.g., apoptosis) that is present in advanced disease. (From Su et al. 2013; adapted, with permission, from Elsevier ©2013.)