Figure 5.

Proposed Zot intracellular signal mediated opening of intestinal tight junctions[146] (printed with permission). 1: Zot interacts with a specific Zot/Zonulin intestinal surface receptor; 2: Leading to protein internalization; 3: Activation of phospholipase C; 4: Hydrolyzes phosphatidyl inositol to release inositol 1,4,5-tris phosphate (PPI-3) and diacylglycerol (DAG), either via DAG or (4a) through the release of intracellular Ca²⁺ via PPI-3; 5: Protein kinase C alpha (PKCα) is then activated; 6: Membrane-associated, activated PKCα catalyzes the phosphorylation of target protein(s); 7: With subsequent polymerization of soluble G-actin in F-actin; 8: This polymerization causes the rearrangement of the tight junctions (TJ) filaments and displacement of proteins [including zonula occludens-1 (ZO-1)]. As a result, intestinal TJ becomes loosened. IP3: Inositol trisphosphate.