Machinery Mediating Kiss‐and‐Run Mechanism of Cell Secretion

Abstract

Secretion is a fundamental cellular process in living organisms, from yeast to cells in humans. Since the 1950's, it was believed that secretory vesicles completely merged with the cell plasma membrane during secretion. While this may occur, the observation of partially empty vesicles in cells following secretion suggests the presence of transient or so called ‘kiss‐and‐run’ mechanism that allows fractional discharge of intra‐vesicular contents during secretion. This proposed mechanism is mediated by a supramolecular cup‐shaped structure at the plasma membrane called ‘porosome’, which enable secretory vesicles to transiently fuse with the plasma membrane, expel a portion of its contents, and disengage. Porosomes range in size from 15 nm in neurons and astrocytes, to 180 nm in endocrine and exocrine cells. Neuronal porosomes are composed of nearly 40 proteins, compared to the 120 nm nuclear pore complex of >500 protein molecules. Porosome structure, its chemical composition, and functional reconstitution into artificial lipid membrane, and the molecular assembly of membrane‐associated t‐SNARE and v‐SNARE proteins in a ring or rosette complex to establish the fusion pore at the porosome base, and the molecular mechanism of secretory vesicle volume increase required for intravesicular content release during cell secretion, collectively provide a molecular understanding of cell secretion, resulting in a paradigm‐shift in our understanding of the process.Support or Funding InformationWork presented in this article was supported in part by the National Science Foundation grants EB00303, CBET1066661 (BPJ)