Occludin (red) and Claudin-1 (green) overlap at the tight junctions (yellow).

Tight junctions are more flexible than researchers realized, as Shen et al. show. The team discovered that proteins are constantly entering and leaving these connections between epithelial cells. The continual remodeling might allow organisms to adjust the permeability of cell layers.

In locations such as the skin and the lining of the intestines, epithelial cells snuggle up to each other to form tight junctions. More than 30 proteins cluster at tight junctions, including ZO-1, which settles on the inner surface of the cell membrane and links the junction to the cytoskeleton. Two other tight junction proteins, occludin and claudin-1, crisscross the membrane. The standard view of tight junctions was that they are static, with the proteins pretty much locked in place.

The researchers had previously observed a subtle flow of tagged occludin molecules in tight junctions, suggesting that proteins enter and leave the junctions or that the entire structure changes position.

To distinguish between these possibilities, Shen et al. used fluorescence recovery after photobleaching and a related technique, fluorescence loss in photobleaching, to track ZO-1, occludin, and claudin-1. ZO-1, they found, was a restless protein that continually cycled between tight junctions and the cytoplasm. Occludin was also a traveler, but it got around through a different mechanism. The protein moved within the junction, the team discovered. It could also enter and leave the junction while remaining within the membrane. Claudin-1, by contrast, was the homebody of the trio, largely staying put.

The work indicates that cells are constantly tinkering with the tight junctions, removing and adding proteins. The researchers speculate that the body alters the lineup of proteins in the junctions to control how much can pass through epithelial layers. For example, after a meal the intestine might loosen the junctions to allow absorption of more nutrients.

Shen, L., et al.
J. Cell Biol.