Figure 3. A lipid-protein model of tight junction structure that may unify ultrastructural, biochemical, and functional data.

This model assumes that the outer leaflets of adjacent plasma membranes fuse at the tight junction. Within these areas, lipids may organize in H_II phase to form inverted micelles and even tubes. These bulges within the fusion site may represent the strands that characterize freeze-fracture images of the tight junction. As discussed in the text, we propose that the membrane fusion and H_II phase transition depend on the unique lipid compoisiton of the tight junction as well as proteins, e.g. claudins, that organize these lipids to establish a barrier while also forming a trans-tight junction ion channel. The model suggests that the claudins actually form the pore that mediates pore pathway flux. Larger, micelles may form a conduit for the leak pathway. Occludin may serve to limit the stability of these micelles and macromolecular flux. This may explain enhanced leak pathway flux upon occludin depletion.