GTP-independent rapid and slow endocytosis at a central synapse

Xu, Jiake; McNeil, Benjamin D.; Wu, Wei; Nees, David W.; Bai, Li; Wu, Ling Gang

doi:10.1038/nn2021

Cited by 80 publications

(122 citation statements)

References 46 publications

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“…A similar scenario has been reported at rodent nerve terminals lacking dynamin 1 (36,75), in which dynamin 3 partially supports vesicle recycling (38,39). It is unclear whether the dynamin-independent endocytosis at some nonsecretory cells (45,71) and nerve terminals (i.e., bulk endocytosis) (40,72,76) also occurs in dynamin 2 KO β cells. Future study using triple dynamin KO cells will shed new light on this question.…”

Section: And E)supporting

confidence: 61%

Dynamin 2 regulates biphasic insulin secretion and plasma glucose homeostasis

Fan¹,

Chen²,

Wu³

et al. 2015

Journal of Clinical Investigation

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Section: And E)supporting

confidence: 61%

Dynamin 2 regulates biphasic insulin secretion and plasma glucose homeostasis

Fan¹,

Chen²,

Wu³

et al. 2015

Journal of Clinical Investigation

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“…α auditory brain stem 10,32 , have shown that episodes of stimulation and exocytosis are followed by endocytosis, thus restoring pre-stimulus conditions. Endocytosis occurs with two distinct time constants, with at least some of the components being highly sensitive to manipulation of intracellular Ca 2+ concentrations [32][33][34] . These results indicate that multiple mechanisms are involved, but they need to be interpreted with some caution, as some of the kinetic components (for example, the rapid component in the calyx of Held) are only observed after very intense, possibly non-physiological stimulation.…”

Section: Box 1 | Presynaptic Organization -Exocytic and Endocytic Zonesmentioning

confidence: 99%

“…Exceptions to this are the rodent calyx of Held, a giant nerve terminal of the auditory brain stem. Presynaptic capacitance measurements of surface membrane area are effectively used to directly follow synaptic vesicle exocytosis and endocytosis 33,34,81 , whereas Ca 2+ can be optically measured and controlled experimentally by uncaging techniques. A drawback of the capacitance technique is that it measures the net change in surface area rather than measuring exocytosis and endocytosis separately.…”

Section: Box 2 | Functional Access To Exocytosis-endocytosis By Electmentioning

confidence: 99%

Protein scaffolds in the coupling of synaptic exocytosis and endocytosis

2011

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Communication between nerve cells largely occurs at chemical synapses -specialized sites of cell-cell contact where electrical signals trigger the exocytic release of neurotransmitter, which in turn activates postsynaptic receptor channels. The efficacy with which such chemical signals are transmitted is crucial for the functioning of the nervous system. Modulation of neurotransmission enables nerve cells to respond to a vast range of stimulus patterns. Synaptic activity can also be tremendously diverse; from the fast synapses of the hippocampus, to slow neuropeptide-containing synapses. Indeed, some signalling pathways are active in the absence of stimulation, such as those involved in the processing of sensory information, which transmit tonically at high rates of up to 100 Hz or more 1,2 .Intriguing questions arise from these facts, including how high rates of neurotransmission can be maintained over long periods of time, and what limits the ability of a given synapse to release neurotransmitter during sustained periods of activity. Recent data indicate that in many synapses, exocytosis of neurotransmitter is coupled to endocytosis, and that synapses have evolved a specialized apparatus of scaffolding proteins to comply with these demands. Such scaffolds aid the temporal and spatial coupling of exocytosis and endocytosis, and are crucial for maintaining rapid neurotransmission during sustained activity 3 .Exocytosis of neurotransmitter is triggered by stimulusinduced calcium influx into the nerve terminal 4,5 and the subsequent fusion of synaptic vesicles with the presynaptic plasma membrane at specialized regions called active zones (BOX 1). Exocytosed synaptic vesicle membrane proteins and lipids in turn are recycled at the endocytic or periactive zone (BOX 1) that surrounds the release site, to restore functional synaptic vesicle pools for reuse and to ensure long-term functionality of the synapse 6-8 (FIG. 1). Depending on the type of synapse and the stimulation frequency, several modes of endocytosis with different time constants -for example, fast and slow endocytosisseem to operate 7,9,10 . Clathrin-mediated endocytosis arguably represents the main pathway of synaptic vesicle endocytosis 6,8,11 , although other modes -for example, fast kiss-and-run exocytosis and endocytosis -could operate in parallel.Although the machineries for exocytic membrane fusion 12,13 and for endocytic retrieval of synaptic vesicle membranes have been studied separately in some detail 6,14 , comparatively little is known about the coupling between exocytosis and endocytosis. Here we synthesize recent data from physiological, morphological and biochemical studies in several model systems into hypothetical models for scaffold-based mechanisms underlying exocytic-endocytic coupling.The synaptic vesicle cycle Synaptic vesicle pools. Some defining features of chemical synapses are the presence of one or several clusters of synaptic vesicles in the presynaptic nerve terminal, and ultrastructural specializations at the pre-and postsy...

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“…In the current issue, Xu et al 3 report an elegant set of experiments that led them to propose that at least some components of synaptic vesicle endocytosis operate independently of dynamin and GTP hydrolysis. The authors took advantage of the intracellular accessibility of the calyx of Held, a large nerve terminal in the auditory brainstem, to examine the dependence of synaptic vesicle endocytosis on dynamin.…”

mentioning

confidence: 99%

“…Xu et al 3 propose that the number of vesicles that can be retrieved via a dynaminand GTPdependent mechanism is fixed, and therefore only vesicles released in excess of this pool are recovered via an alternative mechanism. Vesicles are suggested to be predestined for one form of retrieval, and thus form separate pools (orange versus red vesicles).…”

mentioning

confidence: 99%