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A minireview about the universal molecular machinery and mechanism of secretion in …
Biology Articles » Cell biology » Molecular Machinery and Mechanism of Cell Secretion » Molecular Understanding of Cell Secretion
Fusion pores, or porosomes, are present in all secretory cells examined. From exocrine, endocrine, neuroendocrine cells, to neurons, where membrane-bound secretory vesicles dock and transiently fuse to expel vesicular contents. Porosomes in pancreatic acinar or GH-secreting cells are cup-shaped structures at the plasma membrane, with a 100–150-nm-diameter opening. Membrane-bound secretory vesicles ranging in size from 0.2 to 1.3 µm in diameter dock and fuse at porosomes to release vesicular contents. Following fusion of secretory vesicles at porosomes, only a 20%–35% increase in porosome diameter is demonstrated. It is therefore reasonable to conclude that secretory vesicles transiently dock and fuse at the site. In contrast with accepted belief, if secretory vesicles were to completely incorporate at porosomes, the PM structure would distend much wider than what is observed. Furthermore, if secretory vesicles were to completely fuse at the plasma membrane, there would be a loss in vesicle number following secretion. Examination of secretory vesicles within cells before and after secretion demonstrates that the total number of secretory vesicles remains unchanged following secretion (10, 26). However, the number of empty and partially empty vesicles increases significantly, supporting the occurrence of transient fusion of secretory vesicles at the porosome. Earlier studies in mast cells also demonstrated an increase in the number of spent and partially spent vesicles following stimulation of secretion, without any demonstrable increase in cell size. Similarly, secretory granules are recaptured largely intact after stimulated exocytosis in cultured endocrine cells (22). Other supporting evidence favoring transient fusion is the presence of neurotransmitter transporters at the synaptic vesicle membrane. These vesicle-associated transporters would be of little use if vesicles were to fuse completely at the plasma membrane to be compensatorily endocytosed at a later time. In further support, a recent study reports that single synaptic vesicles fuse transiently and successively without loss of vesicle identity (23). Although the fusion of secretory vesicles at the cell plasma membrane occurs transiently, complete incorporation of membrane at the cell plasma membrane would occur when cells need to incorporate signaling molecules, like receptors, second messengers, or ion channels, at the cell plasma membrane. The discovery of the porosome and an understanding of the molecular mechanism of membrane fusion and the swelling of secretory vesicles required for expulsion of vesicular contents provide an understanding of secretion and membrane fusion in cells at the molecular level. These findings have prompted many laboratories to work in the area and further confirm these findings. Thus, the porosome is a supramolecular structure universally present in secretory cells, from the exocrine pancreas to the neurons, and in the endocrine to neuroendocrine cells, where membrane-bound secretory vesicles transiently dock and fuse to expel vesicular contents. Hence, the secretory process in cells is highly regulated and is orchestrated by a number of ions and biomolecules.
I thank Won Jin Cho for the preparation of the manuscript.
Supported by grants DK-56212 and NS-39918 from the National Institutes of Health (B.P.J).
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