New insights into the control of secretion

Abstract

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.

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Acknowledgements

This work is funded by an Australian Research Council Grant (DP0771481) and a Research Infrastructure Block Grant from The University of Queensland to Peter Thorn.

Figures and Tables

Figure 1 Models for secretory control. (A) in the classical model the entire vesicle content is released, the vesicle collapses and membrane is recovered. (B) in the new model, fusion pore opening and closing regulates content release then either the entire or part of the vesicle membrane is recovered via an unknown mechanism. In some cases it has been shown that part vesicle content can be recovered.

Figure 2 Myosin 2 action in secretion. F-actin coating and myosin 2 phosphorylation appear after fusion. Together we hypothesize these act to maintain the structural integrity of the vesicle and to keep the fusion pore open to allow content loss.

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