Cited by 165Neuroscience and Neuropharmacology ResearchCellular transport and secretionProtein Kinase Regulation and GTPase Signaling

Dynamic Control of Synaptic Vesicle Replenishment and Short-Term Plasticity by Ca2+-Calmodulin-Munc13-1 Signaling

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Lipstein, Noa, Sakaba, Takeshi, Cooper, Benjamin H., Lin, Kun-Han, Strenzke, Nicola, Ashery, Uri, Rhee, Jeong-Seop, Taschenberger, Holger +2 more·2013·Neuron

Abstract

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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Crossref · 10.1016/j.neuron.2013.05.011

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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
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
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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