Synaptotagmin-Mediated Bending of the Target Membrane Is a Critical Step in Ca2+-Regulated Fusion

Hui, Enfu; Johnson, Colin P.; Yao, Jun; Dunning, F. Mark; Chapman, Edwin R.

doi:10.1016/j.cell.2009.05.049

Cited by 268 publications

(451 citation statements)

References 38 publications

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“…Microdomain Ca 2+ is sensed by members of the synaptotagmin family of Ca 2+ -binding C2 domain protein (FIG. 2), which may act on SnARE complexes and on the membrane itself 12,26 . There are a number of other important regulators, including Ras-related Rab proteins and complexins 27 , that impose additional layers of control on the fusion process 13,23 .…”

Section: -2000 Neurotransmitter Moleculesmentioning

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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Section: -2000 Neurotransmitter Moleculesmentioning

confidence: 99%

Protein scaffolds in the coupling of synaptic exocytosis and endocytosis

2011

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“…Synaptotagmin can bind to both syntaxin and SNAP-25, and fast neurotransmitter release requires synaptotagmin (Geppert et al 1994) probably prebound to assembled or partially assembled SNARE complexes (Schiavo et al 1997;Rickman et al 2006) so that Ca 2þ -induced interaction with phospholipids can occur rapidly (Xue et al 2008). It is still under debate how important synaptotagmin is in vesicle docking (de Wit et al 2009) and how it acts at the plasma membrane in fusion itself (Tang et al 2006;Hui et al 2009). Synaptotagmin could act as a brake on fusion that is relieved on Ca 2þ binding or have a positive role in membrane fusion (Chicka et al 2008).…”

Section: Synaptotagmins and Neurotransmitter Releasementioning

confidence: 99%

The Diversity of Calcium Sensor Proteins in the Regulation of Neuronal Function

McCue

Haynes²,

Burgoyne

2010

Cold Spring Harbor Perspectives in Biology

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“…Syt1 is a vesicular protein, consisting of tandem Ca 2ϩ -binding C2 domains and a transmembrane helix (34). Syt1 interacts with the core SNARE complex as well as phospholipids (35)(36)(37)(38)(39). Provided that Syt1 cooperates with the SNARE complex intimately during the moment of fusion, it is difficult to envision how Munc18-1 might gain access to the core complex simultaneously (40).…”

mentioning

confidence: 99%

Synaptotagmin-1 Is an Antagonist for Munc18-1 in SNARE Zippering

Lou

Shin

Yang

et al. 2015

Journal of Biological Chemistry

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Background: The molecular mechanisms of the critical necessity of Munc18-1 protein for neurotransmitter release remain unclear. Results: Synaptotagmin-1 competes with Munc18-1 in SNARE zippering and fusion pore opening. Conclusion: Synaptotagmin-1 wins the tug-of-war in gaining control of the SNAREpin at the moment of membrane fusion. Significance: This work clarifies an ambiguity concerning the Munc18-1 function in neuroexocytosis.

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Synaptotagmin-Mediated Bending of the Target Membrane Is a Critical Step in Ca2+-Regulated Fusion

Cited by 268 publications

References 38 publications

Protein scaffolds in the coupling of synaptic exocytosis and endocytosis

Protein scaffolds in the coupling of synaptic exocytosis and endocytosis

The Diversity of Calcium Sensor Proteins in the Regulation of Neuronal Function

Synaptotagmin-1 Is an Antagonist for Munc18-1 in SNARE Zippering

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