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Vesicle reuse revisited.

Neurons communicate at the synapse by releasing neurotransmitter from synaptic vesicles. After exocytosis, synaptic vesicle membrane and protein are locally recycled for reuse in the presynaptic terminal. The mechanisms involved in the recycling of synaptic vesicle material have yet to be fully resolved (reviewed in ref. 1). The traditional model of vesicle recycling posits that vesicles merge with the plasma membrane and then are later retrieved in perisynaptic regions by endocytosis (2–4). A second model, often referred to as “kiss-and-run” (5), suggests that neurotransmitter is released through a fusion pore that allows the vesicle to release neurotransmitter while retaining its protein and/or lipid (6). By refilling with neurotransmitter, vesicles formed in this manner could potentially become rapidly available for reuse. Evidence for rapid reuse of synaptic vesicles has been found in rat hippocampal neurons (7, 8), yet the contribution of this mechanism to pool recycling remains debated. The work by Li et al. (9) in a recent issue of PNAS introduced new tools and new data to this debate.