RIM-Binding Protein, a Central Part of the Active Zone, Is Essential for Neurotransmitter Release
Open accessAbstract
The molecular machinery mediating the fusion of synaptic vesicles (SVs) at presynaptic active zone (AZ) membranes has been studied in detail, and several essential components have been identified. AZ-associated protein scaffolds are viewed as only modulatory for transmission. We discovered that Drosophila Rab3-interacting molecule (RIM)-binding protein (DRBP) is essential not only for the integrity of the AZ scaffold but also for exocytotic neurotransmitter release. Two-color stimulated emission depletion microscopy showed that DRBP surrounds the central Ca(2+) channel field. In drbp mutants, Ca(2+) channel clustering and Ca(2+) influx were impaired, and synaptic release probability was drastically reduced. Our data identify RBP family proteins as prime effectors of the AZ scaffold that are essential for the coupling of SVs, Ca(2+) channels, and the SV fusion machinery.
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The compartmentalized active zone architecture is reminiscent of protein organization in Drosophila neuromuscular junction and vertebrate ribbon synapses, where vesicles and priming proteins are arrayed around tight clusters of Ca2+ channels.
“The compartmentalized AZ architecture is reminiscent of protein organization in Drosophila neuromuscular junction23 and vertebrate ribbon synapses, where vesicles and priming proteins are arrayed around tight clusters of Ca2+ channels.”
From A trans-synaptic nanocolumn aligns neurotransmitter release to receptors (2016) · cites this paper as [23]
In the absence of RIM-BP, the organization of the active zone is impaired, and the ultrastructural distribution of the ELKS homolog Bruchpilot at active zones is altered.
“The Drosophila experiments additionally revealed that in the absence of RIM-BP, the organization of the active zone was impaired, and the ultrastructural distribution of the ELKS homolog Bruchpilot at active zones was altered, suggesting that RIM-BPs may have additional functions besides assisting RIM in the recruitment of Ca2+ channels.”
From The Presynaptic Active Zone (2012) · cites this paper as Liu et al., 2011
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References 36 · Cited by 306
- Authors
- Liu, K. S. Y., Siebert, M., Mertel, S., Knoche, E., Wegener, S., Wichmann, C., Matkovic, T., Muhammad, K., Depner, H., Mettke, C., Bückers, J., Hell, S. W., Müller, M., Davis, G. W., Schmitz, D., & Sigrist, S. J.
- Affiliations
- Freie Universität Berlin (DE)
- NeuroCure Cluster of Excellence (DE)
- Max Planck Institute for Biophysical Chemistry (DE)
- University of California, San Francisco (US)
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Liu, Karen S. Y.
- Siebert, Matthias
- Mertel, Sara
- Knoche, Elena
- Wegener, Stephanie
- Schmitz, Dietmar
- Sigrist, Stephan J.
- ORCID
- Venue
- Science
- Published
- 2011-12-16
- Volume
- 334
- Issue
- 6062
- Pages
- 1565-1569
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2064575171
- Cited by
- 306
- References
- 36
- Citations by year
- 2026: 3 · 2025: 15 · 2024: 27 · 2023: 23 · 2022: 23 · 2021: 27 · 2020: 18 · 2019: 19 · 2018: 26 · 2017: 18 · 2016: 19 · 2015: 28 · 2014: 27 · 2013: 18 · 2012: 15
- FWCI
- 9.20
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Max Planck Digital Library (submittedVersion, other-oa)
- DZNE Pub (submittedVersion)
- GRO (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- 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 › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- synaptic vesicle fusion, active zone, neurotransmitter release, exocytosis, calcium influx, release probability, Drosophila, synaptic scaffolds
- MeSH terms
- Animals, Carrier Proteins, Drosophila, Male, Mutation, Synapses, Calcium Channels, Presynaptic Terminals, Neurotransmitter Agents, Drosophila Proteins
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