A Munc13/RIM/Rab3 tripartite complex: from priming to plasticity?
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alpha-RIMs and Munc13s are active zone proteins that control priming of synaptic vesicles to a readily releasable state, and interact with each other via their N-terminal sequences. The alpha-RIM N-terminal sequence also binds to Rab3s (small synaptic vesicle GTPases), an interaction that regulates presynaptic plasticity. We now demonstrate that alpha-RIMs contain adjacent but separate Munc13- and Rab3-binding sites, allowing formation of a tripartite Rab3/RIM/Munc13 complex. Munc13 binding is mediated by the alpha-RIM zinc-finger domain. Elucidation of the three-dimensional structure of this domain by NMR spectroscopy facilitated the design of a mutation that abolishes alpha-RIM/Munc13 binding. Selective disruption of this interaction in the calyx of Held synapse decreased the size of the readily releasable vesicle pool. Our data suggest that the ternary Rab3/RIM/Munc13 interaction approximates synaptic vesicles to the priming machinery, providing a substrate for presynaptic plasticity. The modular architecture of alpha-RIMs, with nested binding sites for Rab3 and other targets, may be a general feature of Rab effectors that share homology with the alpha-RIM N-terminal sequence.
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Rim2 interacts with Rab3A and Munc13-1, and also interacts with the cAMP-sensing protein cAMP-GEFII/Epac2.
“Like Rim1, Rim2 interacts with Rab3A (496) and Munc13-1 (160, 750). It also interacts with the cAMP-sensing protein cAMP-GEFII (also known as Epac2) (496, 615).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [160]
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Protein backbone angle restraints from searching a database for chemical shift and sequence homology
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- Authors
- Dulubova, I., Lou, X., Lu, J., Huryeva, I., Alam, A., Schneggenburger, R., Südhof, T. C., & Rizo, J.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Max Planck Society (DE)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Rizo, Josep
- Venue
- The EMBO Journal
- Published
- 2005-07-28
- Volume
- 24
- Issue
- 16
- Pages
- 2839-2850
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1187938
- OpenAlex
- W2125278970
- Cited by
- 289
- References
- 3
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 6 · 2023: 14 · 2022: 24 · 2021: 7 · 2020: 8 · 2019: 14 · 2018: 15 · 2017: 13 · 2016: 10 · 2015: 12 · 2014: 19 · 2013: 16 · 2012: 17
- FWCI
- 7.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Welch Foundation
- American Heart Association
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS40944, R01NS040944)
- 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 › Protein Kinase Regulation and GTPase Signaling
- Keywords
- Munc13, Rab3, synaptic vesicle priming, readily releasable pool, presynaptic plasticity, active zone proteins, zinc finger, calyx of Held, Rab effectors, synaptic vesicle exocytosis
- MeSH terms
- Amino Acid Sequence, Binding Sites, Calorimetry, Electrophysiology, Escherichia coli, Glutathione Transferase, Humans, Models, Molecular, Molecular Sequence Data, Nerve Tissue Proteins, Synaptic Vesicles, Mutagenesis, Sequence Alignment, GTP-Binding Proteins, Nuclear Magnetic Resonance, Biomolecular, rab3 GTP-Binding Proteins, Multiprotein Complexes
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