Tight junction protein 1 (ZO-1) and tight junction complex (ZO-1)

Tight junction protein 1 (ZO-1), also known as TJP1, is a high-molecular-weight scaffolding protein that serves as a primary organizer of the tight junction (TJ) complex in epithelial and endothelial cells (UniProt P39447). It belongs to the membrane-associated guanylate kinase (MAGUK) family and functions by anchoring transmembrane proteins, such as claudins, occludin, and junctional adhesion molecules (JAMs), to the underlying actin cytoskeleton (PubMed: 21248165). This structural linkage is vital for the formation and maintenance of the paracellular barrier, which regulates the passage of ions, water, and macromolecules between cells. In many diseases, including inflammatory bowel disease, celiac disease, and various cancers, the integrity of the ZO-1/TJ complex is compromised, leading to increased barrier permeability or "leaky" epithelia (PubMed: 16112588). Therapeutic strategies targeting this complex often focus on stabilizing ZO-1 or inhibiting pathways that trigger its disassembly, such as the zonulin pathway. For instance, larazotide acetate is a peptide drug designed to prevent TJ opening by inhibiting zonulin-mediated ZO-1 redistribution, thereby treating conditions like celiac disease (ClinicalTrials.gov: NCT03569007).

Other names

Tight junction protein 1TJP1Zonula occludens protein 1ZO-1

Antagonism of zonulin-induced tight junction disassembly and stabilization of the ZO-1/actin cytoskeletal link