Barriers to exocytotic vesicle discharge

Regulated exocytosis, a universal process of eukaryotic cells, involves the merging between the vesicle membrane and the plasma membrane, plays a key role in cell-to-cell communication, particularly in the release of hormones and neurotransmitters. There are a number of barriers a vesicle needs to pass to discharge vesicle content to the extracellular space. At the pre-fusion site vesicles need to be transported to the sites on the plasma membrane where the merger may begin. Classically cytoskeleton was considered an important barrier for vesicle translocation and was thought to be disintegrated to allow vesicle access to the plasma membrane [1]. However, it was considered later that cytoskeletal elements may also play a role at the post-fusion stage, promoting the vesicle merger with the plasma membrane and fusion pore expansion [4,22,23]. In this Special Issue of Cell Calcium entitled "Regulated Exocytosis", the authors address outstanding issues related to vesicle chemical messenger release by regulated exocytosis, including that related to the question whether vesicle content discharge is complete or only partial upon the merging of the vesicle membrane with the plasma membrane triggered by Ca²⁺. Among processes that limit vesicle discharge at the post-fusion stage is the accumulation of cholesterol in some vesicles [19], a process that has recently been associated with cell aging [20].