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Protein Quantification at the Single Vesicle Level Reveals That a Subset of Synaptic Vesicle Proteins Are Trafficked with High Precision
Open accessAbstract
Protein sorting represents a potential point of regulation in neurotransmission because it dictates the protein composition of synaptic vesicles, the organelle that mediates transmitter release. Although the average number of most vesicle proteins has been estimated using bulk biochemical approaches (Takamori et al., 2006), no information exists on the intervesicle variability of protein number, and thus on the precision with which proteins are sorted to vesicles. To address this, we adapted a single molecule quantification approach (Mutch et al., 2007) and used it to quantify both the average number and variance of seven integral membrane proteins in brain synaptic vesicles. We report that four vesicle proteins, SV2, the proton ATPase, Vglut1, and synaptotagmin 1, showed little intervesicle variation in number, indicating they are sorted to vesicles with high precision. In contrast, the apparent number of VAMP2/synaptobrevin 2, synaptophysin, and synaptogyrin demonstrated significant intervesicle variability. These findings place constraints on models of protein function at the synapse and raise the possibility that changes in vesicle protein expression affect vesicle composition and functioning.
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“SV2A is a promising biomarker of synaptic density as it is ubiquitously and, for the most part, homogeneously present in synaptic vesicles [47] with low variation in copy number per vesicle [66].”
From Challenges and rewards of in vivo synaptic density imaging, and its application to the study of depression (2025) · cites this paper as [66]
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Metadata
- Authors
- Mutch, S. A., Kensel-Hammes, P., Gadd, J. C., Fujimoto, B. S., Allen, R. W., Schiro, P. G., Lorenz, R. M., Kuyper, C. L., Kuo, J. S., Bajjalieh, S. M., & Chiu, D. T.
- Affiliations
- University of Washington (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-01-26
- Volume
- 31
- Issue
- 4
- Pages
- 1461-1470
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3078718
- OpenAlex
- W2069765655
- Cited by
- 185
- References
- 39
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 16 · 2023: 12 · 2022: 17 · 2021: 16 · 2020: 16 · 2019: 8 · 2018: 7 · 2017: 10 · 2016: 11 · 2015: 5 · 2014: 10 · 2013: 12 · 2012: 16
- FWCI
- 7.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Directorate for Biological Sciences
- University of California, Davis
- National Institute of Neurological Disorders and Stroke (U24NS050606, R01NS052637, NS052637)
- 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
- synaptic vesicle proteins, protein sorting, vesicle composition, SV2, VGLUT1, synaptotagmin-1, synaptophysin, H+-ATPase, neurotransmitter release, synaptic transmission
- MeSH terms
- Animals, Brain, Membrane Proteins, Synaptic Vesicles, Rats, Sprague-Dawley, Protein Transport, Rats, In Vitro Techniques
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