Rab3A Is Involved in Transport of Synaptic Vesicles to the Active Zone in Mouse Brain Nerve Terminals
Open accessAbstract
The rab family of GTP-binding proteins regulates membrane transport between intracellular compartments. The major rab protein in brain, rab3A, associates with synaptic vesicles. However, rab3A was shown to regulate the fusion probability of synaptic vesicles, rather than their transport and docking. We tested whether rab3A has a transport function by analyzing synaptic vesicle distribution and exocytosis in rab3A null-mutant mice. Rab3A deletion did not affect the number of vesicles and their distribution in resting nerve terminals. The secretion response upon a single depolarization was also unaffected. In normal mice, a depolarization pulse in the presence of Ca 2+induces an accumulation of vesicles close to and docked at the active zone (recruitment). Rab3A deletion completely abolished this activity-dependent recruitment, without affecting the total number of vesicles. Concomitantly, the secretion response in the rab3A-deficient terminals recovered slowly and incompletely after exhaustive stimulation, and the replenishment of docked vesicles after exhaustive stimulation was also impaired in the absence of rab3A. These data indicate that rab3A has a function upstream of vesicle fusion in the activity-dependent transport of synaptic vesicles to and their docking at the active zone.
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Several genes implicated in cocaine withdrawal (e.g., Nrgn, Cck, Rab3a) have widely known neuronal function.
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- Authors
- Leenders, A. G. M., da Silva, F. H. L., Ghijsen, W. E. J. M., & Verhage, M.
- Affiliations
- University of Amsterdam (NL)
- Graduate School for the Neurosciences, Institute of Neurobiology, University of Amsterdam, 1098 SM The Netherlands,
- Utrecht University (NL)
- ORCID
- Verhage, Matthijs
- Venue
- Molecular Biology of the Cell
- Published
- 2001-10
- Volume
- 12
- Issue
- 10
- Pages
- 3095-3102
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC60158
- OpenAlex
- W2114442092
- Cited by
- 115
- References
- 32
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 2 · 2023: 8 · 2022: 5 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 6 · 2013: 5 · 2012: 4
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular Biology of the Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- Rab3A, synaptic vesicle transport, active zone, synaptic vesicle docking, exocytosis, Rab GTPases, presynaptic terminals, vesicle replenishment, synaptic vesicle fusion
- MeSH terms
- Animals, Brain, Calcium, Microscopy, Electron, Mutation, Neurons, Subcellular Fractions, Synaptic Vesicles, Gene Deletion, Mice, Knockout, GTP-Binding Proteins, rab3A GTP-Binding Protein, Mice
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