The Synaptic Vesicle Cycle Revisited: New Insights into the Modes and Mechanisms - PubMed (original) (raw)

Review

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

Natali L Chanaday et al. J Neurosci. 2019.

Abstract

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.

Copyright © 2019 the authors.

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Figures

Figure 1.

Figure 1.

Classical view of the SV cycle. Action potentials trigger fusion of SVs at the active zone. After formation of the fusion pore, resulting in neurotransmitter release, two options are possible: the pore can reclose via kiss-and-run (K&R) or it can expand irreversibly, leading to full collapse. Compensating for full-collapse fusion, specific SV proteins are recruited by adaptor proteins at the periactive zone, triggering CME. Dynamin mediates vesicle scission, after which SVs are uncoated and refilled with neurotransmitters before being returned to the vesicle cluster.

Figure 2.

Figure 2.

Modern view of the SV cycle. A, During low activity levels, SVs are recruited to the RRP from the reserve/resting pool and fuse at the active zone, after which they may be retrieved via one of several mechanisms: (1) the fusion pore may reclose by kiss-and-run, (2) ultrafast endocytosis at the periactive zone can retrieve endocytic vesicles that rapidly fuse with synaptic endosomes from which SVs regenerate in a clathrin-dependent manner, or (3) CME can generate SVs from the plasma membrane in certain circumstances, after which vesicle uncoating is necessary for the vATPase to acidify the lumen triggering concurrent neurotransmitter (NT) refilling by transporters. After refilling, SVs can be recruited back to the cluster, where they are segregated into functional pools. B, At high activity levels, many SVs are mobilized and exocytosed by full-collapse fusion. This activates ADBE, which retrieves large areas of membrane generating bulk endosomes from which SVs regenerate.

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