New insights into the control of secretion.

Vesicular secretion is a fundamental process in the body with vesicle fusion releasing vesicle contents to the outside. This process called exocytosis is usually thought of as leading to an all-or-none release of content; regulation of secretory output dependent on regulating the numbers of fused vesicles. However, it is well established that the fusion pore that forms when the vesicle membrane fuses with the cell membrane is dynamic. More recent evidence indicates the dynamic opening and closing, and the size of the fusion pore, are limiting factors to the release of vesicle content. What remains unclear is whether these fusion pore behaviors are under cellular control and therefore relevant to cell physiology.Accumulating evidence over the last two years points to myosin 2 as one regulator of fusion pore behavior. This is interesting since myosin 2 activity is in turn controlled by kinases and phosphatases, well known to be under cellular control. We conclude that fusion pore behavior is likely a genuine control point for vesicle content release. This leads to a model for secretion with secretory output controlled not only by the numbers of vesicles fused but also by the regulation of the behavior of individual vesicles.