RIM1α forms a protein scaffold for regulating neurotransmitter release at the active zone
Abstract
Neurotransmitters are released by synaptic vesicle fusion at the active zone. The active zone of a synapse mediates Ca2+-triggered neurotransmitter release, and integrates presynaptic signals in regulating this release. Much is known about the structure of active zones and synaptic vesicles, but the functional relation between their components is poorly understood. Here we show that RIM1alpha, an active zone protein that was identified as a putative effector for the synaptic vesicle protein Rab3A, interacts with several active zone molecules, including Munc13-1 (ref. 6) and alpha-liprins, to form a protein scaffold in the presynaptic nerve terminal. Abolishing the expression of RIM1alpha in mice shows that RIM1alpha is essential for maintaining normal probability of neurotransmitter release, and for regulating release during short-term synaptic plasticity. These data indicate that RIM1alpha has a central function in integrating active zone proteins and synaptic vesicles into a molecular scaffold that controls neurotransmitter release.
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Mutations in synapsins, Munc13, and RIMs alter short-term plasticity in a manner independent of the first two sets of mechanisms.
“Mutations in several proteins associated with the release machinery alter short-term plasticity in a manner independent of the first two sets of mechanisms, for example mutations in synapsins (Rosahl et al., 1995), Munc13 (Augustin et al., 1999), and RIMs (Schoch et al., 2002).”
From The Presynaptic Active Zone (2012) · cites this paper as Schoch et al., 2002
A targeted Rims1 mutation in the mouse leads to increased postsynaptic density and impaired associative learning, memory, and cognition.
“A targeted Rims1 mutation in the mouse leads to increased postsynaptic density and impaired associative learning as well as memory and cognition deficits (Powell et al., 2004; Schoch et al., 2002)”
From De Novo Gene Disruptions in Children on the Autistic Spectrum (2012) · cites this paper as Schoch et al., 2002
RIMS1 has a regulatory role in synaptic-vesicle exocytosis modulating synaptic transmission and plasticity.
“RIMS1 has a regulatory role in synaptic-vesicle exocytosis modulating synaptic transmission and plasticity.51”
From Convergence of genes and cellular pathways dysregulated in autism spectrum disorders (2014) · cites this paper as [51]
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Self-citation
- Authors
- Schoch, S., Castillo, P. E., Jo, T., Mukherjee, K., Geppert, M., Wang, Y., Schmitz, F., Malenka, R. C., & Südhof, T. C.
- Affiliations
- Howard Hughes Medical Institute (US)
- Albert Einstein College of Medicine (US)
- Max Planck Institute of Experimental Medicine (DE)
- Max Planck Society (DE)
- Stanford Medicine (US)
- Corresponding author
- Südhof, Thomas C.
- ORCID
- Venue
- Nature
- Published
- 2002-01
- Volume
- 415
- Issue
- 6869
- Pages
- 321-326
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1964189494
- Cited by
- 579
- References
- 28
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 13 · 2023: 14 · 2022: 15 · 2021: 19 · 2020: 13 · 2019: 17 · 2018: 19 · 2017: 27 · 2016: 19 · 2015: 24 · 2014: 20 · 2013: 28 · 2012: 24
- FWCI
- 13.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Institutes of Health
- 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 › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- active zone, neurotransmitter release, synaptic vesicle fusion, protein scaffolds, Munc13-1, Rab3A, short-term plasticity, release probability, presynaptic terminals
- MeSH terms
- Animals, Brain, Mutation, Nerve Tissue Proteins, Neuronal Plasticity, Phosphoproteins, Protein Binding, Dizocilpine Maleate, Presynaptic Terminals, Mice, Knockout, Neurotransmitter Agents, GTP-Binding Proteins, COS Cells, Protein Isoforms, rab3A GTP-Binding Protein, Macromolecular Substances, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Mice, In Vitro Techniques
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