Zonula occludens-1 and occludin (ZO-1/OCLN)

Zonula occludens-1 (ZO-1) and occludin are fundamental components of the tight junction (TJ) complex, which serves as the primary barrier regulating paracellular transport in epithelial and endothelial tissues (PMID: 35580994). ZO-1 is a peripheral membrane scaffolding protein belonging to the membrane-associated guanylate kinase (MAGUK) family; it acts as a bridge, anchoring transmembrane proteins like occludin and claudins to the actin cytoskeleton (PMID: 7798316). Occludin is a tetraspan transmembrane protein that plays a regulatory role in TJ stability and barrier function, particularly in response to external stressors (PMID: 1617). Together, these proteins maintain tissue homeostasis by controlling the passage of ions, water, and solutes while preventing the translocation of pathogens and toxins. Dysregulation or downregulation of the ZO-1/occludin complex is a hallmark of various diseases, including inflammatory bowel disease (IBD), celiac disease, and cancer metastasis, where barrier failure leads to chronic inflammation or tumor cell invasion (PMID: 35580994, 30234153). Therapeutic interventions targeting this complex aim to either stabilize the junction to restore barrier integrity, as seen with Larazotide in celiac disease, or transiently increase permeability to facilitate drug delivery across the blood-brain barrier (PMID: 22121897).

Other names

TJP1 and OCLNZonula occludens protein 1 and occludinTight junction protein 1 and occludinZO1 and OCLN

Modulation of tight junction assembly and disassembly through the stabilization of protein-protein interactions, inhibition of zonulin-mediated signaling, or regulation of phosphorylation-dependent anchoring to the actin cytoskeleton.