Synaptotagmin Increases the Dynamic Range of Synapses by Driving Ca2+-Evoked Release and by Clamping a Near-Linear Remaining Ca2+ Sensor
Open accessAbstract
Ca²+-evoked transmitter release shows a high dynamic range over spontaneous release. We investigated the role of the Ca²+ sensor protein, Synaptotagmin2 (Syt2), in both spontaneous and Ca²+-evoked release under direct control of presynaptic [Ca²+](i), using an in vivo rescue approach at the calyx of Held. Re-expression of Syt2 rescued the highly Ca²+ cooperative release and suppressed the elevated spontaneous release seen in Syt2 KO synapses. This latter release clamping function was partially mediated by the poly-lysine motif of the C₂B domain. Using an aspartate mutation in the C₂B domain (D364N) in which Ca²+ triggering was abolished but release clamping remained intact, we show that Syt2 strongly suppresses the action of another, near-linear Ca²+ sensor that mediates release over a wide range of [Ca²+](i). Thus, Syt2 increases the dynamic range of synapses by driving release with a high Ca²+ cooperativity, as well as by suppressing a remaining, near-linear Ca²+ sensor.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Syt1 also clamps the frequency of miniature spontaneous events.
“In addition to its role in evoked synchronous release, Syt1 also clamps the frequency of miniature spontaneous events11–13.”
From Architecture of the synaptotagmin–SNARE machinery for neuronal exocytosis (2015) · cites this paper as [13]
The primary Syt1-SNARE interface is critical for the role of Syt1 as a Ca2+ sensor of evoked release, but is not required for spontaneous release in neurons.
“Together, these observations support the notion that the primary Syt1-SNARE interface is critical for the role of Syt1 as a Ca2+ sensor of evoked release, but that this Syt1-SNARE interface is not required for spontaneous release in neurons, consistent with the differential effect of Syt1 mutations on spontaneous and evoked release11–13.”
From Architecture of the synaptotagmin–SNARE machinery for neuronal exocytosis (2015) · cites this paper as [13]
Cites
Synaptotagmin I: A major Ca2+ sensor for transmitter release at a central synapse
Geppert, M., Goda, Y., Hammer, R. E., Li, C., Rosahl, T. W., Stevens, C. F., & Südhof, T. C. (1994) · Cell · doi:10.1016/0092-8674(94)90556-8 · Cited by 1,483 · see citing works
Kerr, A. M., Reisinger, E., & Jonas, P. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800621105 · Cited by 75 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The mechanisms and functions of spontaneous neurotransmitter release
Kavalali, E. T. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3875 · Cited by 486 · see citing works
Architecture of the synaptotagmin–SNARE machinery for neuronal exocytosis
Zhou, Q., Lai, Y., Bacaj, T., Zhao, M., Lyubimov, A. Y., Uervirojnangkoorn, M., Zeldin, O. B., Brewster, A. S., Sauter, N. K., Cohen, A. E., et al. (2015) · Nature · doi:10.1038/nature14975 · Cited by 348 · see citing works
Bradberry, M. M., & Chapman, E. R. (2022) · The Journal of Physiology · doi:10.1113/jp282601 · Cited by 16 · see citing works
Turecek, J., & Regehr, W. G. (2020) · eLife · doi:10.7554/elife.61672 · Cited by 13 · see citing works
“…are present, but asynchronous if they are absent (Turecek and Regehr, 2019), consistent with a role of Syt1/2 in release synchrony at other synapses (Bacaj et al., 2013; Chen et al., 2017; DiAntonio and Schwarz, 1994; Geppert et al., 1994; Kochubey and Schneggenburger, 2011; Xu et al., 2007).”
Background
- Authors
- Kochubey, O., & Schneggenburger, R.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Schneggenburger, Ralf
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 69
- Issue
- 4
- Pages
- 736-748
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2142809407
- Cited by
- 109
- References
- 2
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 5 · 2020: 9 · 2019: 9 · 2018: 7 · 2017: 7 · 2016: 7 · 2015: 11 · 2014: 14 · 2013: 7 · 2012: 7
- FWCI
- 4.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- spontaneous release, calyx of Held, C2B domain, presynaptic calcium
- MeSH terms
- Animals, Animals, Newborn, Asparagine, Aspartic Acid, Auditory Pathways, Brain Stem, Calcium, Electric Stimulation, Functional Laterality, Mice, Transgenic, Mutation, Synaptic Transmission, Synapses, Cochlear Nucleus, Nonlinear Dynamics, Presynaptic Terminals, Patch-Clamp Techniques, Green Fluorescent Proteins, Synaptotagmin II, Mice, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
