Porosome: the secretory portal

'It seems terribly wasteful that, during the release of hormones and neurotransmitters from a cell, the membrane of a vesicle should merge with the plasma membrane to be retrieved for recycling only seconds or minutes later.' - Erwin Neher, Nature 1993;363:497-498. This insightful statement so appropriately put, clearly reflected on the perception that secretory vesicles completely merge at the cell plasma membrane, failing to justify the generation of partially empty secretory vesicles in cells following secretion. A rational cellular mechanism would employ the transient fusion of secretory vesicles at the cell plasma membrane without compromising vesicle integrity, combined with vesicle retrieval following partial discharge of contents, to generate such partially empty vesicles following secretion. This hypothesis was finally confirmed with the serendipitous discovery of the porosome almost 16 years ago. The porosome has been demonstrated to be the universal secretory portal in cells and is present at the cell plasma membrane. In the past decade, the composition of the porosome, its dynamics, its structure at nanometer resolution in realtime using atomic force and electron microscopy, and its functional reconstitution into artificial lipid membrane, has resulted in a paradigm shift and a molecular understanding of the secretory process in cells. A brief background on porosome discovery, and our current understanding of its structure and function is summarized in this Minireview.