Tight junctions: from simple barriers to multifunctional molecular gates

Key Points Tight junctions are intercellular adhesion complexes in epithelia and endothelia that control paracellular permeability. This paracellular diffusion barrier is semipermeable: it is size- and charge-selective. Paracellular ion permeability at tight junctions is largely determined by their claudin composition. Claudins are a family of transmembrane proteins that are thought to form gated ion-selective paracellular pores through the paracellular diffusion barrier. Tight junctions form the border between the apical and basolateral cell surface domains in polarized epithelia, and support the maintenance of cell polarity by restricting intermixing of apical and basolateral transmembrane components. Tight junctions are an integral component of the evolutionarily conserved signalling mechanisms that control epithelial-cell polarization and the formation of morphologically and functionally distinct apical domains. Tight junctions form bidirectional signalling platforms that receive signals from the cell interior, which regulate their assembly and function, and that transduce signals to the cell interior to control cell proliferation, migration, differentiation and survival. Tight junctions are part of an interconnected network of adhesion complexes that also includes adherens junctions and focal adhesions. These adhesion complexes crosstalk through direct protein–protein interactions as well as by transmitting signals to each other that influence their assembly and function. Tight junctions are barriers between epithelial and endothelial cells that regulate the diffusion of molecules across tissues; they also contribute to cell polarity and serve as signalling platforms. Recent findings have broadened our understanding of tight junction organization, assembly and function. Epithelia and endothelia separate different tissue compartments and protect multicellular organisms from the outside world. This requires the formation of tight junctions, selective gates that control paracellular diffusion of ions and solutes. Tight junctions also form the border between the apical and basolateral plasma-membrane domains and are linked to the machinery that controls apicobasal polarization. Additionally, signalling networks that guide diverse cell behaviours and functions are connected to tight junctions, transmitting information to and from the cytoskeleton, nucleus and different cell adhesion complexes. Recent advances have broadened our understanding of the molecul