The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
A Clamping Mechanism Involved in SNARE-Dependent Exocytosis
Abstract
During neurotransmitter release at the synapse, influx of calcium ions stimulates the release of neurotransmitter. However, the mechanism by which synaptic vesicle fusion is coupled to calcium has been unclear, despite the identification of both the core fusion machinery [soluble N -ethylmaleimide–sensitive factor attachment protein receptor (SNARE)] and the principal calcium sensor (synaptotagmin). Here, we describe what may represent a basic principle of the coupling mechanism: a reversible clamping protein (complexin) that can freeze the SNAREpin, an assembled fusion-competent intermediate en route to fusion. When calcium binds to the calcium sensor synaptotagmin, the clamp would then be released. SNARE proteins, and key regulators like synaptotagmin and complexin, can be ectopically expressed on the cell surface. Cells expressing such “flipped” synaptic SNAREs fuse constitutively, but when we coexpressed complexin, fusion was blocked. Adding back calcium triggered fusion from this intermediate in the presence of synaptotagmin.
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Cites
SNAP receptors implicated in vesicle targeting and fusion
Söllner, T., Whiteheart, S. W., Brunner, M., Erdjument-Bromage, H., Geromanos, S., Tempst, P., & Rothman, J. E. (1993) · Nature · doi:10.1038/362318a0 · Cited by 3,237
Self-citationSNAREpins: Minimal Machinery for Membrane Fusion
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Self-citationCrystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution
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Synaptotagmin I: A major Ca2+ sensor for transmitter release at a central synapse
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Synaptotagmin I functions as a calcium regulator of release probability
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Microdomains of High Calcium Concentration in a Presynaptic Terminal
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Complexins Regulate a Late Step in Ca2+-Dependent Neurotransmitter Release
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Complexins: Cytosolic proteins that regulate SNAP receptor function
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Cited by
Membrane Fusion: Grappling with SNARE and SM Proteins
Südhof, T. C., & Rothman, J. E. (2009) · Science · doi:10.1126/science.1161748 · Cited by 2,027
Self-citationNeurotransmitter Release: The Last Millisecond in the Life of a Synaptic Vesicle
Südhof, T. C. (2013) · Neuron · doi:10.1016/j.neuron.2013.10.022 · Cited by 1,197
Mechanisms of membrane fusion: disparate players and common principles
Martens, S., & McMahon, H. T. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2417 · Cited by 710
Rizo, J., & Rosenmund, C. (2008) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1450 · Cited by 538
Selective Activation of Cognate SNAREpins by Sec1/Munc18 Proteins
Shen, J., Tareste, D. C., Paumet, F., Rothman, J. E., & Melia, T. J. (2007) · Cell · doi:10.1016/j.cell.2006.12.016 · Cited by 484
Self-citation
Metadata
- Authors
- Giraudo, C. G., Eng, W. S., Melia, T. J., & Rothman, J. E.
- Venue
- Science
- Published
- 2006-08-04
- Volume
- 313
- Issue
- 5787
- Pages
- 676-680
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2063253418
- Cited by
- 368
- References
- 34
- FWCI
- 15.60
- Type
- journal article
- Language
- en
- Open access
- closed
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