Kiss and patch up

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Damage to the digestive tract from partially digested food is repaired by calcium-dependent mucus secretion and resealed with spent membrane vesicles.

The cell lining of the gastrointestinal tract is continually damaged by mechanical stresses and scratching by partially digested food as it traverses the gut. Potentially, this could have fatal consequences for the cells, but the digestive tract has evolved two defence mechanisms: the formation of membrane patches that plaster over holes in the membrane, and the secretion of a lubricating mucus that cushions the membrane against further abrasions. Miyake et al. have now shown that during cell injury, both of these processes are rapidly activated to protect the gastrointestinal tract.


Coupling of mucus secretion and membrane repair. Adapted from figure 7 in the highlighted paper.

Miyake et al. monitored mucus secretion using fluorescently labelled lectins that bind to the glycoproteins found in mucus granules. Wounding the mucosal cells, by repetitively drawing them up through a syringe, induced the release of lectins into the surrounding medium. The amount of lectin secretion increased with the amount of cell injury but was inhibited in the absence of calcium, which is known to be an important regulator of membrane-fusion events.

The authors developed a second method for assessing plasma membrane resealing after wounding. Cells were incubated with a lipophilic fluorescent dye that labels the plasma membrane. When cell membranes were punctured by a laser insult, the cytoplasm was quickly labelled by the dye in the absence of calcium. In the presence of calcium, no intracellular labelling was observed, which indicated that the plasma membrane was rapidly resealed following injury.

By combining these two techniques, Miyake et al. conclusively showed that membrane resealing occurs as a consequence of mucus secretion. After injury, cells that lacked cytosolic staining by the lipophilic dye were abundantly labelled on their membranes by fluorescent lectins, indicating that mucus secretion had occurred. Furthermore, cells that survived plasma-membrane disruption were depleted of intracellular mucus, which was instead secreted. Therefore, it seems that an increase in calcium promotes the secretion of mucus-laden vesicles. It is the 'spent' vesicle membranes themselves that subsequently remain on the plasma membrane and patch over the hole.

Importantly, when these experiments were repeated in segments of rat colon, the same conclusions were reached. This work has raised some key questions. For example, how is calcium involved in mucus secretion and membrane resealing? And, could these 'healing' processes be defective in pathological conditions of the gastrointestinal tract, as has been demonstrated to be the case for skeletal muscle?

James Pickett

References

Miyake, K. et al. Disruption-induced mucus secretion: repair and protection. PLoS Biol. 4, 1525 - 1531 (2006) | Article | PubMed |
Bansal, D. et al. Defective membrane repair in dysferlin-deficient muscular dystrophy. Nature 423, 168–172 (2003) | Article | PubMed |