Chapter 5 Molecular structure and regulation of tight junctions

Abstract

This chapter describes the molecular structure and regulation of tight junctions. Solute and water transport in the intestine requires both active transcellular transport mechanisms and the presence of a paracellular seal between two epithelial cells; tight junctions provide this seal. The tight junction was defined physiologically and microscopically during the 1960s and 1970s, long before any bio-chemical components were identified. This lack of biochemical insight impeded the rationalization of the junction's regulated barrier properties. The tight junction is located as a continuous gasket-like seal at the most apical region of the lateral cell membranes. In 1986, ZO-1, the first tight junction protein, was identified; now there are more than two dozen known junction-associated proteins. This has allowed recent attempts to describe the biochemical basis of tight-junction function. The chapter reviews the methods commonly used to study tight-junction physiology and known protein components, with special attention to those suspected of having a role in the organization or regulation of the junction. The issues that are specifically relevant to tight junctions in the gastrointestinal tract, such as the molecular mechanisms of bacterial toxins that contribute to diarrhea by disrupting the paracellular barrier, are also discussed in the chapter.