Synaptic Vesicle Endocytosis in Different Model Systems

Abstract

Neurotransmission in complex animals depends on a choir of functionally distinct synapses releasing neurotransmitters in a highly coordinated manner. During synaptic signaling, vesicles fuse with the plasma membrane to release their contents. The rate of vesicle fusion is high and can exceed the rate at which synaptic vesicles can be re-supplied by distant sources. Thus, local compensatory endocytosis is needed to replenish the synaptic vesicle pools. Over the last four decades, various experimental methods and model systems have been used to study the cellular and molecular mechanisms underlying synaptic vesicle cycle. Clathrin-mediated endocytosis is thought to be the predominant mechanism for synaptic vesicle recycling. However, recent studies suggest significant contribution from other modes of endocytosis, including fast compensatory endocytosis, activity-dependent bulk endocytosis, ultrafast endocytosis, as well as kiss-and-run. Currently, it is not clear whether a universal model of vesicle recycling exist for all types of synapses. It is possible that each synapse type employs a particular mode of endocytosis. Alternatively, multiple modes of endocytosis operate at the same synapse, and the synapse toggles between different modes depending on its activity level. Here we compile review and research articles based on well-characterized model systems: frog neuromuscular junctions, C. elegans neuromuscular junctions, Drosophila neuromuscular junctions, lamprey reticulospinal giant axons, goldfish retinal ribbon synapses, the calyx of Held, and rodent hippocampal synapses. We will compare these systems in terms of their known modes and kinetics of synaptic vesicle endocytosis, as well as the underlying molecular machineries. We will also provide the future development of this field.

Balancing presynaptic release and endocytic membrane retrieval at hair cell ribbon synapses

“…Consistent with the findings from other tissues (reviewed in Refs ), brief depolarizations that predominantly recruit the RRP, activate a slow mode of endocytosis, which declines linearly with a rate of approximately 1–2 fF/s and is limited in speed . In IHCs, this component of endocytosis can be selectively targeted (but not completely inhibited) by pharmacological inhibitors of CME and a missense mutation in dynamin1 .…”

Hsc70 Ameliorates the Vesicle Recycling Defects Caused by Excess α-Synuclein at Synapses

“…The phenotype reported is consistent with an impairment of synaptic vesicle recycling via inhibition of CME and possibly bulk endocytosis. Because CME is a predominant mechanism for locally recycling synaptic vesicles at many synapses (Heuser and Reese, 1973;Granseth et al, 2006;Heerssen et al, 2008;Walsh et al, 2018), and because clathrin-mediated vesicle budding is also critical for other modes of SV recycling such as ultrafast and bulk endocytosis (Watanabe et al, 2014;Gan and Watanabe, 2018;Chanaday et al, 2019), we set out to determine in this study exactly how excess ␣-synuclein impacts clathrin-mediated processes at synapses and to identify the underlying mechanisms.…”

Endocytosis in proliferating, quiescent and terminally differentiated cells

“…FEME is not constitutive, but leads to a prompt formation of tubulo-vesicular endocytic carriers following the activation of several receptors by their cognate ligands (reviewed in Watanabe and Boucrot, 2017;Ferreira and Boucrot, 2018). Ultrafast endocytosis at the synapse shares features with FEME in that it also relies on dynamin, endophilin, actin and synaptojanin, but is at least one order of magnitude faster (reviewed in Gan and Watanabe, 2018;Watanabe and Boucrot, 2017). Following intense stimulations, macropinocytosis and ADBE in neurons lead to the formation of large (≥0.5 µm) carriers that take up substantial amounts of extracellular material and plasma membrane (Cousin, 2017;Mercer and Helenius, 2012).…”