An extended release for surfactant

Most think of exocytosis as an instantaneous process that once started cannot be fine-tuned. But on page 279, Haller et al. describe the exocytosis of surfactant from specialized lung cells (alveolar type II cells), and find that the degree and rate of pore expansion can be modified, thus controlling the rate of release of this vital agent from open pores.The authors gauge the extent of pore opening by adding a dye, and comparing the rate of its accumulation in either free surfactant or surfactant that remains trapped in open pores. The relative rates give a measure of the opening of the pores, and indicate that opening can be slow initially before a later expansion or, occasionally, retraction. Pores can remain open for as long as several hours. Continuous measurements of pore behavior were made by using an intermediate laser strength that balances photobleaching of dye with replenishment by new dye accumulation.

Surfactant comes in a big hydrophobic glob, so it is perhaps not surprising that it takes some time to unspool it through a fusion pore. But post-fusion regulation might be relevant to other exocytic cargos, such as those that are only slowly released from proteoglycan tethers or other matrices, or even untethered cargos present in vesicles that flicker open and closed only briefly.

Haller et al. point to calcium as a major regulator of post-fusion pore behavior. Calcium is released by both of the two stimuli that are known to potentiate surfactant release from alveolar cells—ATP and mechanical stretch from breathing—and in the current study, an increase in intracellular free calcium dilates the fusion pores. The calcium could be acting on the cytoskeleton to reduce cortical tension around fusion pores, thus allowing their expansion, but the details of this regulation remain unknown. ▪