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Functional Interaction of the Active Zone Proteins Munc13-1 and RIM1 in Synaptic Vesicle Priming
Open accessAbstract
Synaptic neurotransmitter release is restricted to active zones, where the processes of synaptic vesicle tethering, priming to fusion competence, and Ca2+-triggered fusion are taking place in a highly coordinated manner. We show that the active zone components Munc13-1, an essential vesicle priming protein, and RIM1, a Rab3 effector with a putative role in vesicle tethering, interact functionally. Disruption of this interaction causes a loss of fusion-competent synaptic vesicles, creating a phenocopy of Munc13-1-deficient neurons. RIM1 binding and vesicle priming are mediated by two distinct structural modules of Munc13-1. The Munc13-1/RIM1 interaction may create a functional link between synaptic vesicle tethering and priming, or it may regulate the priming reaction itself, thereby determining the number of fusion-competent vesicles.
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“Although Munc13s do not have transmembrane domains, Munc13-1 in synapses appears to be tightly anchored to the AZ via scaffold proteins [62,63] and interacts with components of the sub-membranous cytoskeleton [64], rendering it effectively insoluble [65].”
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 [62]
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Self-citationRim is a putative Rab3 effector in regulating synaptic-vesicle fusion
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Long-term culture of astrocytes attenuates the readily releasable pool of synaptic vesicles
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Molecular and functional architecture of striatal dopamine release sites
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Self-citationELKS1 localizes the synaptic vesicle priming protein bMunc13-2 to a specific subset of active zones
Kawabe, H., Mitkovski, M., Kaeser, P. S., Hirrlinger, J., Opazo, F., Nestvogel, D., Kalla, S., Fejtova, A., Verrier, S. E., Bungers, S. R., et al. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201606086 · Cited by 50
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Self-citationDisentangling the roles of RIM and Munc13 in synaptic vesicle localization and neurotransmission
Zarebidaki, F., Camacho, M., Brockmann, M. M., Trimbuch, T., Herman, M. A., & Rosenmund, C. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.1922-20.2020 · Cited by 37
Self-citationVariability in the Munc13-1 content of excitatory release sites.
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Self-citationKim, O., Okamoto, Y., Kaufmann, W. A., Brose, N., Shigemoto, R., & Jonas, P. (2024) · PLOS Biology · doi:10.1371/journal.pbio.3002879 · Cited by 15
Self-citationControl of Munc13-1 Activity by Autoinhibitory Interactions Involving the Variable N-terminal Region
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Metadata
- Authors
- Betz, A., Thakur, P., Junge, H. J., Ashery, U., Rhee, J.-S., Scheuss, V., Rosenmund, C., Rettig, J., & Brose, N.
- Affiliations
- Max Planck Institute of Experimental Medicine (DE)
- Max Planck Institute for Biophysical Chemistry (DE)
- Corresponding author
- Brose, Nils
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2001-04
- Volume
- 30
- Issue
- 1
- Pages
- 183-196
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1994381304
- Cited by
- 425
- References
- 36
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 7 · 2023: 17 · 2022: 23 · 2021: 12 · 2020: 14 · 2019: 10 · 2018: 13 · 2017: 25 · 2016: 8 · 2015: 11 · 2014: 15 · 2013: 14 · 2012: 15
- FWCI
- 8.40
- 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)
- 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 › Molecular Biology › Extracellular vesicles in disease
- Keywords
- Munc13-1, RIM1, synaptic vesicle priming, active zone, synaptic vesicle tethering, synaptic vesicle fusion, neurotransmitter release, protein-protein interaction
- MeSH terms
- Animals, Binding Sites, Cells, Cultured, DNA-Binding Proteins, Fungal Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Synaptic Transmission, Neurons, Synaptic Vesicles, Zinc Fingers, Sequence Homology, Amino Acid, Alternative Splicing, Protein Structure, Tertiary, Presynaptic Terminals, Neurotransmitter Agents, Protein Isoforms, Two-Hybrid System Techniques, rab3A GTP-Binding Protein
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