Molecular basis of the core structure of tight junctions

Abstract

The morphological feature of tight junctions (TJs) fits well with their functions. The core of TJs is a fibril-like proteinaceous structure within the lipid bilayer, the so-called TJ strands. TJ strands in apposing plasma membranes associate with each other to eliminate the intercellular space. A network of paired TJ strands generates a continuous belt that circumscribes each cell to establish the diffusion barrier to the solutes in the paracellular pathway throughout the cellular sheet. Identification and characterization of TJ-associated proteins during the last two decades has unveiled the nature of TJ strands and how they are spatially organized. The interplay between integral membrane proteins, claudins, and cytoplasmic plaque proteins, ZO-1/ZO-2, is critical for TJ formation and function.

Figure 1.

Thin section of TJs of mouse epididymis epithelial cells. TJs are defined as close contacts between plasma membranes of adjacent cells. Bar, 100 nm.

Figure 2.

Freeze-fracture replica of TJs of mouse intestinal epithelial cells. TJs appear as anastomosing fibrils, namely, TJ strands, on P-face (arrow) or complementary grooves on E-face (arrowhead) in glutaraldehyde-fixed specimens. Bar, 200 nm.

Figure 3.

Freeze-fracture replica of tTJs in MDCK cells. At tricellular corners, the most apical elements of the horizontal TJ strands from both sides (arrowheads) attach to form the central seal and extend vertically in the basal direction. Short, horizontal strands connect with the central seal. Bar, 100 nm.

Figure 4.

The membrane-spanning model of claudins and the domain organization of claudin-binding plaque proteins. Claudins contain four transmembrane domains. The conserved amino acid residues in the first extracellular loop are indicated. The PDZ domain binding motif is located at the carboxyl terminus, which is known to bind to PDZ-domains in ZO-1, ZO-2, ZO-3, MUPP1, and PATJ (stars). (GUK) guanylate kinase domain; (L27) LIN2, 7 homology domain; (U5) unique 5 region; (U6) unique 6 region. U6 contains the acidic region.