The synaptic vesicle cluster: A source of endocytic proteins during neurotransmitter release

Over the past few years significant progress has been achieved in understanding the molecular steps underlying the fusion and recycling of vesicles at central synapses. It still remains unclear, however, how the fusion event is linked with vesicle membrane retrieval. Several factors promoting the transition from exo- to endocytosis have been extensively studied, including levels of intracellular Ca2+, the synaptic proteins involved at both sides of the vesicle cycle, posttranslational modification of endocytic proteins, and the lipid composition of recycled membranes. Recent studies in glutamate synapses indicate that vesicle clusters accumulated at the sites of synaptic contacts have a more complex organization than has previously been thought. Many endocytic proteins reside in the vesicle pool at rest and undergo cycles of migration between the active and periactive zones during synaptic activity. We propose that the local migration of endocytic proteins triggered by Ca2+ influx into the nerve terminal functions as one of the molecular mechanisms coupling exo- and endocytosis in synapses.