Exocytotic Fusion Pore Intermediates of Dense-Core Vesicles

Abstract

Regulated exocytosis is a multistage process involving a merger between the vesicle and the plasma membranes, leading to the formation of a fusion pore, a channel, through which secretions are released from the vesicle to the cell exterior. A stimulus may influence the pore by either dilating it completely (full-fusion exocytosis) or mediating a reversible closure (transient exocytosis). In neurons, these transitions are short-lived and not accessible for experimentation. However, in some neuroendocrine cells, initial fusion pores may reopen several hundred times, indicating their stability. Moreover, these pores are too narrow to pass luminal molecules to the extracellular space, but their diameter can dilate upon stimulation. To explain the stability of the initial narrow fusion pores, anisotropic membrane constituents with non-axisymmetrical shape were proposed to accumulate in the fusion pore membrane. Although the nature of these is unclear, they may consist of lipids and proteins, including SNAREs, which may facilitate and regulate the pre- and post-fusional stages of exocytosis.