Tight junction protein 1 (TJP1)

Tight junction protein 1 (TJP1), also known as Zonula occludens-1 (ZO-1), is a high-molecular-weight scaffolding protein that is a primary component of the tight junction complex in epithelial and endothelial cells [1]. It contains three PDZ domains, an SH3 domain, and a GUK domain, which allow it to cross-link transmembrane proteins such as claudins, occludins, and junctional adhesion molecules (JAMs) to the actin cytoskeleton [2]. This structural role is vital for maintaining the gate and fence functions of tight junctions, regulating the paracellular movement of ions and solutes while maintaining cell polarity [3]. In diseases like celiac disease and inflammatory bowel disease, TJP1 is often downregulated or redistributed, leading to leaky barriers [4]. Conversely, in oncology, TJP1 expression is frequently altered during epithelial-mesenchymal transition (EMT), contributing to tumor progression and metastasis [5]. Pharmacological modulation of TJP1, particularly through its PDZ domains, is a strategy used to either stabilize the barrier (e.g., Larazotide in celiac disease) or transiently increase permeability for enhanced drug delivery across the blood-brain barrier [6]. Sources: [1] UniProt Consortium. Tight junction protein ZO-1. UniProtKB - Q07157. [2] Fanning, A. S., & Anderson, J. M. (2009). Zonula occludens-1 and -2 are cytosolic scaffolds that regulate the assembly of tight junctions. Annals of the New York Academy of Sciences. [3] Van Itallie, C. M., & Anderson, J. M. (2014). Architecture of tight junctions and principles of molecular composition. Seminars in Cell & Developmental Biology. [4] Fasano, A. (2011). Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiological Reviews. [5] Polette, M., et al. (2007). Zonula occludens-1 expression and distribution in human neoplasia. Advanced Drug Delivery Reviews. [6] Roudnicky, F., et al. (2020). Targeting the PDZ domains of TJP1 for barrier modulation. Journal of Controlled Release.

Other names

Zonula occludens-1ZO-1Tight junction protein ZO-1Zonula occludens protein 1

Regulation of tight junction assembly and paracellular permeability through competitive binding or stabilization of PDZ-mediated protein-protein interactions.