Fusion pores and their control of neurotransmitter and hormone release

Ca(2+)-triggered exocytosis functions broadly in the secretion of chemical signals, enabling neurons to release neurotransmitters and endocrine cells to release hormones. The biological demands on this process can vary enormously. Although synapses often release neurotransmitter in a small fraction of a millisecond, hormone release can be orders of magnitude slower. Vesicles usually contain multiple signaling molecules that can be released selectively and conditionally. Cells are able to control the speed, concentration profile, and content selectivity of release by tuning and tailoring exocytosis to meet different biological demands. Much of this regulation depends on the fusion pore—the aqueous pathway by which molecules leave a vesicle and move out into the surrounding extracellular space. Studies of fusion pores have illuminated how cells regulate secretion. Furthermore, the formation and growth of fusion pores serve as a readout for the progress of exocytosis, thus revealing key kinetic stages that provide clues about the underlying mechanisms. Herein, we review the structure, composition, and dynamics of fusion pores and discuss the implications for molecular mechanisms as well as for the cellular regulation of neurotransmitter and hormone release.