Tight junction protein 1 (ZO-1) (ZO-1)

Tight junction protein 1 (ZO-1) is a vital peripheral membrane scaffolding protein and a member of the membrane-associated guanylate kinase (MAGUK) family. It acts as a primary molecular bridge at the cytoplasmic surface of intercellular tight junctions, linking transmembrane proteins like claudins and occludin to the perijunctional actin cytoskeleton. This structural role is essential for maintaining the "gate" and "fence" functions of epithelial and endothelial barriers, which regulate paracellular permeability and preserve cell polarity. Beyond its scaffolding function, ZO-1 participates in critical signal transduction pathways, including Hippo signaling, to regulate cell proliferation, differentiation, and tissue morphogenesis. In clinical contexts, the downregulation or redistribution of ZO-1 is a hallmark of barrier dysfunction in diseases such as celiac disease and inflammatory bowel disease, while its overexpression is often linked to epithelial-mesenchymal transition and metastasis in several cancers. Therapeutic efforts involve tight junction modulators like larazotide acetate, which acts as a zonulin antagonist to stabilize the ZO-1 complex and restore intestinal barrier integrity.

Other names

TJP1Zonula occludens protein 1Zonula occludens-1ZO1220-kD peripheral membrane protein

Modulation of tight junction assembly and stabilization of the ZO-1 scaffolding complex at the cell membrane to restore or regulate epithelial barrier integrity.