Dynamic Control of Synaptic Vesicle Replenishment and Short-Term Plasticity by Ca2+-Calmodulin-Munc13-1 Signaling
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Short-term synaptic plasticity, the dynamic alteration of synaptic strength during high-frequency activity, is a fundamental characteristic of all synapses. At the calyx of Held, repetitive activity eventually results in short-term synaptic depression, which is in part due to the gradual exhaustion of releasable synaptic vesicles. This is counterbalanced by Ca(2+)-dependent vesicle replenishment, but the molecular mechanisms of this replenishment are largely unknown. We studied calyces of Held in knockin mice that express a Ca(2+)-Calmodulin insensitive Munc13-1(W464R) variant of the synaptic vesicle priming protein Munc13-1. Calyces of these mice exhibit a slower rate of synaptic vesicle replenishment, aberrant short-term depression and reduced recovery from synaptic depression after high-frequency stimulation. Our data establish Munc13-1 as a major presynaptic target of Ca(2+)-Calmodulin signaling and show that the Ca(2+)-Calmodulin-Munc13-1 complex is a pivotal component of the molecular machinery that determines short-term synaptic plasticity characteristics.
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Forskolin slightly reduces the distance between CaV2.1 Ca2+ channels and Munc13-1.
“Furthermore, we discovered that forskolin slightly reduced the distance between CaV2.1 (P/Q-type) Ca2+ channels and Munc13-1, an essential vesicle priming protein and putative marker of primed vesicles [14,40–45].”
From Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons (2024) · cites this paper as [44]
Munc13-1/2 are putative markers of primed vesicles.
“and Munc13-1/2, putative markers of primed vesicles [14,42–45,60,61].”
From Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons (2024) · cites this paper as [44]
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- Authors
- Lipstein, N., Sakaba, T., Cooper, B. H., Lin, K.-H., Strenzke, N., Ashery, U., Rhee, J.-S., Taschenberger, H., Neher, E., & Brose, N.
- Affiliations
- Tel Aviv University (IL)
- Doshisha University (JP)
- Max Planck Institute of Experimental Medicine (DE)
- Max Planck Institute for Biophysical Chemistry (DE)
- Universitätsmedizin Göttingen (DE)
- Corresponding author
- Brose, Nils
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 79
- Issue
- 1
- Pages
- 82-96
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2089616767
- Cited by
- 165
- References
- 71
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 8 · 2023: 10 · 2022: 14 · 2021: 13 · 2020: 11 · 2019: 10 · 2018: 11 · 2017: 21 · 2016: 11 · 2015: 18 · 2014: 17 · 2013: 5
- FWCI
- 8.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- GRO (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (24300144)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- Munc13-1, Ca2+/calmodulin signaling, synaptic vesicle replenishment, short-term plasticity, short-term depression, calyx of Held, synaptic vesicle priming, presynaptic neurotransmitter release, recovery from depression, high-frequency stimulation, knock-in mice
- MeSH terms
- Animals, Calcium, Calmodulin, Mice, Transgenic, Nerve Tissue Proteins, Synaptic Transmission, Neuronal Plasticity, Synapses, Synaptic Vesicles, Signal Transduction, Mice
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