The fusion of two membranes into one is an event shared by intracellular trafficking, fertilization, tissue formation, and viral infection (Earp et al., 2005; Jahn et al., 2003; Mohler et al., 2002). On a structural level, fusion results in the unification of the lipid and protein components of the two membranes and the intermixing of the volumes initially bound by them. During membrane fusion, the proximal leaflets of the two membranes merge first, whereas the distal membrane leaflets remain separate until the opening of a fusion pore (Chernomordik and Kozlov, 2005). This intermediate stage, called hemifusion, is a critical event shared by exocytosis, protein trafficking, and viral entry. Kozlov et al. (2010) have promoted the idea that both fusion and fission of membranes results from protein-driven stress. Pore dynamics determine the efficiency of vesicular cargo release and vesicle retrieval which are generated by competition between pore expansion and constriction. Pharmacology and mutation experiments suggest that expansion and constriction are mediated by F-actin-dependent membrane tension and calcium/dynamin, respectively (Shin et al. 2018).

Many substances (neurotransmitters, proteins, complex carbohydrates, small molecules such as ATP) in eukaryotes are sequestered in vesicles which then fuse with the plasma membrane releasing to the extracellular medium the intra-vesicular contents. The vesicles can then either reform or remain associated with the plasma membrane. In the latter case, the lipids flow from the vesicle into the plasma membrane. Two modes of fusion—full collapse fusion (FCF) and kiss-and-run (K&R)—reported in central nervous system (CNS) neurons—have been reported. Park et al. (2012) reported three-dimensional, real-time tracking of quantum dot-loaded single synaptic vesicles. Determination of the time, position, and mode of fusion revealed that vesicles starting close to their ultimate fusion sites tended to fuse earlier than those positioned farther away. The mode of fusion depended on the prior motion of vesicles, with long-dwelling vesicles preferring kiss-and-run rather than full-collapse fusion. Kiss-and-run fusion events were concentrated near the center of the synapse, whereas full-collapse fusion events were broadly spread.

Recently, fusion has been shown to initiate by formation of a pore complex of various pore sizes.