Kinetic efficiency of endocytosis at mammalian CNS synapses requires synaptotagmin I

Nicholson-Tomishima, Karin; Ryan, Timothy A.

doi:10.1073/pnas.0406968101

Cited by 135 publications

(126 citation statements)

References 32 publications

(45 reference statements)

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“…Previous studies have noted that the rate of synaptic vesicle endocytosis is slower in Syt1 KO animals (Poskanzer et al, 2003(Poskanzer et al, , 2006NicholsonTomishima and Ryan, 2004) but an elevation in [Ca 2ϩ ] e rescues the endocytic defect caused by a Syt1 mutant with low Ca 2ϩ affinity (Poskanzer et al, 2006). However, due to the evidence that there exist multiple forms of endocytosis, such as CME, kissand-run, and bulk endocytosis in synapses (Wu et al, 2007), and that the contribution of each form of endocytosis in synaptic vesicle endocytosis varies markedly in different conditions such as when Ca 2ϩ level is changed (Wu et al, 2009), the mechanism for the defect in synaptic vesicle endocytosis from Syt1 KO animals (Poskanzer et al, 2003(Poskanzer et al, , 2006Nicholson-Tomishima and Ryan, 2004) remains uncertain. Our results identify that, in contrast to WT cells, the Ca 2ϩ dependence of fission dynamics during CME is abolished in Syt1 KO cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

Synaptotagmin 1 Is Necessary for the Ca²⁺Dependence of Clathrin-Mediated Endocytosis

Yao¹,

Rao²,

Varga³

et al. 2012

J. Neurosci.

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The role of Ca 2ϩ in synaptic vesicle endocytosis remains uncertain due to the diversity in various preparations where several forms of endocytosis may contribute variably in different conditions. Although recent studies have demonstrated that Ca 2ϩ is important for clathrin-mediated endocytosis (CME), the mechanistic role of Ca 2ϩ in CME remains to be elucidated. By monitoring CME of single vesicles in mouse chromaffin cells with cell-attached capacitance measurements that offer millisecond time resolution, we demonstrate that the dynamics of vesicle fission during CME is Ca 2ϩ dependent but becomes Ca 2ϩ independent in synaptotagmin 1 (Syt1) knock-out cells. Our results thus suggest that Syt1 is necessary for the Ca 2ϩ dependence of CME.

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Section: Discussionmentioning

confidence: 99%

Synaptotagmin 1 Is Necessary for the Ca²⁺Dependence of Clathrin-Mediated Endocytosis

Yao¹,

Rao²,

Varga³

et al. 2012

J. Neurosci.

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“…For example, neurons lacking the exocytic SnARE protein synaptobrevin 2 show a strong defect in synaptic vesicle reformation following high sucrose-induced depletion of the RRP 77 . Furthermore, synaptic vesicle endocytosis is slowed approximately twofold or threefold in synaptotagmin 1 knockout mice 78 . Endocytic defects are also observed in mice lacking the synaptotagmin 1-associated synaptic vesicle proteins synaptic vesicle glycoprotein 2A and synaptic vesicle glycoprotein 2B 79 .…”

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

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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“…Since synaptotagmin-1 is an essential modulator of Ca 2+ -dependent neurosecretion (Tucker and Chapman, 2002), its mislocalization presumably contributes to the physiological impairments in stoned mutants. Synaptotagmin-1 is also suggested to be directly involved in the endocytic pathway of the synaptic vesicle cycle (Poskanzer et al, 2003;Nicholson-Tomishima and Ryan, 2004). Therefore, the mislocalization of synaptotagmin-1 in stoned mutants might directly participate in perturbing synaptic vesicle recycling.…”

Section: Introductionmentioning

confidence: 99%

Stoned B mediates sorting of integral synaptic vesicle proteins

Mohrmann¹,

Matthies²,

Woodruff³

et al. 2008

Neuroscience

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A continuous supply of fusion-competent synaptic vesicles is essential for sustainable neurotransmission. Drosophila mutations of the dicistronic stoned locus disrupt normal vesicle cycling and cause functional deficits in synaptic transmission. Although both Stoned A and B proteins putatively participate in reconstituting synaptic vesicles, their precise function is still unclear. Here we investigate the effects of progressive depletion of Stoned B (STNB) on the release properties of neuromuscular synapses using a novel set of synthetic STNB hypomorphic alleles. Decreasing neuronal STNB expression to ≤35% of wildtype level causes a strong reduction in EJC amplitude at low stimulation frequencies and a marked slowing in synaptic depression during high-frequency stimulation, suggesting vesicle depletion is attenuated by decreased release probability. Recovery from synaptic depression after prolonged stimulation is also decelerated in mutants, indicating a delayed recovery of fusion-ready vesicles. These phenotypes appear not to be due to a diminished vesicle population, since the docked vesicle pool is ultrastructurally unaffected, and the total number of vesicles is only slightly reduced in these hypomorphs, unlike lethal stoned mutants. Therefore, we conclude that STNB not only functions as an essential component of the endocytic complex for vesicle reconstitution, as previously proposed, but also regulates the competence of recycled vesicles to undergo fusion. In support of such role of STNB, synaptic levels of the vesicular glutamate transporter (vGLUT) and synaptotagmin-1 are strongly reduced with diminishing STNB function, while other synaptic proteins are largely unaffected. We conclude that STNB organizes the endocytic sorting of a subset of integral synaptic vesicle proteins thereby regulating the fusion-competence of the recycled vesicle.

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Kinetic efficiency of endocytosis at mammalian CNS synapses requires synaptotagmin I

Cited by 135 publications

References 32 publications

Synaptotagmin 1 Is Necessary for the Ca²⁺Dependence of Clathrin-Mediated Endocytosis

Synaptotagmin 1 Is Necessary for the Ca²⁺Dependence of Clathrin-Mediated Endocytosis

Protein scaffolds in the coupling of synaptic exocytosis and endocytosis

Stoned B mediates sorting of integral synaptic vesicle proteins

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Kinetic efficiency of endocytosis at mammalian CNS synapses requires synaptotagmin I

Cited by 135 publications

References 32 publications

Synaptotagmin 1 Is Necessary for the Ca2+Dependence of Clathrin-Mediated Endocytosis

Synaptotagmin 1 Is Necessary for the Ca2+Dependence of Clathrin-Mediated Endocytosis

Protein scaffolds in the coupling of synaptic exocytosis and endocytosis

Stoned B mediates sorting of integral synaptic vesicle proteins

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Synaptotagmin 1 Is Necessary for the Ca²⁺Dependence of Clathrin-Mediated Endocytosis

Synaptotagmin 1 Is Necessary for the Ca²⁺Dependence of Clathrin-Mediated Endocytosis