The Synaptic Vesicle Cycle Revisited:New Insights into the Modes and Mechanisms

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of Neuroscience 39(42), (2019): 8209-8216, doi:10.1523/JNEUROSCI.1158-19.2019.Neurotransmission is sustained by endocytosis and refilling of synaptic vesicles (SVs) locally within the presynapse. Until recently, a consensus formed that after exocytosis, SVs are recovered by either fusion pore closure (kiss-and-run) or clathrin-mediated endocytosis directly from the plasma membrane. However, recent data have revealed that SV formation is more complex than previously envisaged. For example, two additional recycling pathways have been discovered, ultrafast endocytosis and activity-dependent bulk endocytosis, in which SVs are regenerated from the internalized membrane and synaptic endosomes. Furthermore, these diverse modes of endocytosis appear to influence both the molecular composition and subsequent physiological role of individual SVs. In addition, previously unknown complexity in SV refilling and reclustering has been revealed. This review presents a modern view of the SV life cycle and discusses how neuronal subtype, physiological temperature, and individual activity patterns can recruit different endocytic modes to generate new SVs and sculpt subsequent presynaptic performance.This work was supported by: Schram-Stiftung T287/25457 and Deutsche Forschungsgemeinschaft (Emmy Noether Young Investigator Award MI-1702/1 to I.M.); the Wellcome Trust (204954/Z/16/Z to M.A.C.); the National Science Foundation (1727260 to S.W.), the National Institutes of Health (NINDS DP2 NS111133 and R01 NS105810 to S.W.); the McKnight Foundation (S.W.); the Sloan Foundation (S.W.); and the National Institutes of Health (NINDS/NIA R01 NS078165 to J.R.M. and NIMH R01 MH066198 to Dr. Ege Kavalali, which supports N.L.C.). We thank Dragomir Milovanovic for helpful comments on this manuscript.2020-04-1

How do you recognize and reconstitute a synaptic vesicle after fusion? [version 1; referees: 3 approved]

Synaptic vesicle recycling is essential for sustained and reliable neurotransmission. A key component of synaptic vesicle recycling is the synaptic vesicle biogenesis process that is observed in synapses and that maintains the molecular identity of synaptic vesicles. However, the mechanisms by which synaptic vesicles are retrieved and reconstituted after fusion remain unclear. The complex molecular composition of synaptic vesicles renders their rapid biogenesis a daunting task. Therefore, in this context, kiss-and-run type transient fusion of synaptic vesicles with the plasma membrane without loss of their membrane composition and molecular identity remains a viable hypothesis that can account for the fidelity of the synaptic vesicle cycle. In this article, we discuss the biological implications of this problem as well as its possible molecular solutions