Molecular Events in Membrane Fusion Occurring During Mast Cell Degranulation

Abstract

Mast cells provide an unusually attractive system for considering the molecular events involved in membrane fusion. When either antigen, (1) anti-immunoglobulin (Ig) antibody (2) or concanavalin A (con A) (3,11) bind to and cross link cytophilic IgE (9,11,13) on the surface of sensitized mast cells in the presence of extracellular Ca²⁺ (7), they induce exocytotic histamine release (degranulation) within seconds (l6). Degranulation involves the fusion of granule membranes with plasma membrane (and subsequently with other granules) followed by the opening of the granule contents to the extracellular space (3,12). Histamine contained in the granules is released by a process of cation exchange; histamine bound to granule matrix exchanges mainly with extra-cellular Na⁺ (16). Histamine release leads to easily recognisable ultra-structural changes in the granules, including loss of electron density and homogeneity, and an increase in size (3,4,12). Since the cells degranulate all over their surface there is always an extensive amount of membrane interaction and fusion taking place. They are, therefore, an excellent system in which to study the molecular events that occur during membrane fusion.