Epidermal growth factor receptor and Protease-activated receptor 2 complex (EGFR/PAR2 complex)

The zonulin receptor, molecularly identified as a complex involving the Epidermal Growth Factor Receptor (EGFR) and Protease-Activated Receptor 2 (PAR2), is a primary regulator of paracellular permeability in the intestinal epithelium (Sturgeon & Fasano, 2016). Upon binding its ligand zonulin (the human analogue of the Vibrio cholerae zonula occludens toxin), the receptor complex initiates a signaling cascade involving phospholipase C and protein kinase C (Fasano, 2011). This activation leads to the phosphorylation of tight junction proteins such as zonula occludens-1 (ZO-1) and occludin, resulting in the contraction of the perijunctional actin-myosin ring and the subsequent opening of tight junctions (Tripathi et al., 2009). While this process is a physiological mechanism for nutrient and fluid transport, its dysregulation is a hallmark of 'leaky gut' and is strongly associated with the pathogenesis of autoimmune disorders like celiac disease and type 1 diabetes (Fasano, 2012). Therapeutic targeting of this receptor, most notably with the peptide antagonist larazotide acetate, aims to prevent zonulin-induced barrier disruption and the translocation of luminal antigens into the submucosa (Gopalakrishnan et al., 2012).

Other names

Zonulin receptorZot receptorZonula occludens toxin receptorPre-haptoglobin 2 receptorHP2 receptor

Competitive antagonism of zonulin binding to the receptor complex, preventing the downstream signaling that leads to tight junction disassembly and increased paracellular permeability.