Endothelial tight junction complex (TJ complex)

The endothelial tight junction (TJ) complex is a specialized multiprotein structure located at the apical-lateral membrane of endothelial cells, primarily responsible for regulating paracellular permeability and maintaining the vascular barrier [1, 2]. It consists of transmembrane proteins such as claudins (notably claudin-5 in the brain), occludin, and junctional adhesion molecules (JAMs), which are anchored to the actin cytoskeleton by cytoplasmic scaffolding proteins like zonula occludens (ZO-1, ZO-2, ZO-3) [4, 7, 14]. This complex is critical for the integrity of the blood-brain barrier (BBB) and other vascular beds, preventing the uncontrolled passage of solutes, pathogens, and inflammatory cells into tissues [11, 15]. In various diseases, including sepsis, cancer metastasis, and neurodegeneration, the TJ complex is disrupted, leading to edema and tissue damage [7, 18, 20]. Conversely, therapeutic strategies aim to either stabilize these junctions to treat vascular leak or transiently open them to facilitate the delivery of macromolecular drugs across barriers like the BBB [3, 5, 8]. The regulation of this complex involves intricate signaling pathways, including Rho GTPases and various kinases, which modulate the assembly and tension of the junctional proteins [2, 17]. Understanding and targeting the endothelial tight junction complex remains a pivotal area of research for improving drug delivery and managing vascular-related pathologies [5, 21].

Other names

Zonula occludensParacellular barrierInterendothelial tight junctionsBlood-brain barrier tight junctions

Modulation of paracellular permeability through the regulation of transmembrane protein interactions and cytoskeletal anchoring [3, 5, 17].