RIM determines Ca2+ channel density and vesicle docking at the presynaptic active zone
Open accessAbstract
At presynaptic active zones, neurotransmitter release is initiated by the opening of voltage-gated Ca²+ channels close to docked vesicles. The mechanisms that enrich Ca²+ channels at active zones are, however, largely unknown, possibly because of the limited presynaptic accessibility of most synapses. Here, we have established a Cre-lox based conditional knockout approach at a presynaptically accessible central nervous system synapse, the calyx of Held, to directly study the functions of RIM proteins. Removal of all RIM1/2 isoforms strongly reduced the presynaptic Ca²+ channel density, revealing a role of RIM proteins in Ca²+ channel targeting. Removal of RIMs also reduced the readily releasable pool, paralleled by a similar reduction of the number of docked vesicles, and the Ca²+ channel-vesicle coupling was decreased. Thus, RIM proteins co-ordinately regulate key functions for fast transmitter release, enabling a high presynaptic Ca²+ channel density and vesicle docking at the active zone.
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Binding of the RIM PDZ-domain to Ca2+ channels is essential for recruiting Ca2+ channels to active zones.
“In contrast, the binding of the RIM PDZ-domain to Ca2+ channels is essential for recruiting Ca2+ channels to active zones (Kaeser et al., 2011; Han et al., 2011).”
From The Presynaptic Active Zone (2012) · cites this paper as Han et al., 2011
Deletion of RIM leads to a decrease in the number of vesicles available for release.
“In keeping with this idea, deletion of RIM leads to a decrease in the number of vesicles available for release (252).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [252]
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- Authors
- Han, Y., Kaeser, P. S., Südhof, T. C., & Schneggenburger, R.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Schneggenburger, Ralf
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 69
- Issue
- 2
- Pages
- 304-316
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3259453
- OpenAlex
- W2135414903
- Cited by
- 354
- References
- 3
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 10 · 2023: 15 · 2022: 19 · 2021: 17 · 2020: 18 · 2019: 17 · 2018: 30 · 2017: 34 · 2016: 26 · 2015: 32 · 2014: 27 · 2013: 38 · 2012: 31
- FWCI
- 15.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 928 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Howard Hughes Medical Institute
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (122496)
- National Institute on Drug Abuse (K01DA029044)
- 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 › Ion channel regulation and function
- Keywords
- active zone, vesicle docking, readily releasable pool, calyx of Held, neurotransmitter release, conditional knockout
- MeSH terms
- Animals, Brain Stem, Calcium, Synaptic Transmission, Synaptic Vesicles, Calcium Channels, Presynaptic Terminals, Mice, Knockout, Neurotransmitter Agents, GTP-Binding Proteins, Protein Isoforms, rab3 GTP-Binding Proteins, Mice
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