Secretory vesicles transiently dock and fuse at the porosome to discharge contents during cell secretion.

In contrast with the observation in electron micrographs of partially empty vesicles in cells following secretion, it has been believed since the 1950s that during cell secretion, secretory vesicles completely merge at the cell plasma membrane, resulting in the diffusion of intravesicular contents to the cell exterior and the compensatory retrieval of the excess membrane by endocytosis. In the interim, a large body of work has been published arguing both for and against the complete merger of secretory vesicle membrane at the cell plasma membrane during secretion. The only definitive determination of the mechanism of cell secretion remained in its direct observation at nanometre resolution in live cells. In the past decade, this finally became a reality through the power and scope of the atomic force microscope, which has made it possible to resolve a major conundrum in cell biology. This paradigm shift in our understanding of cell secretion is briefly outlined here.