Single-vesicle imaging reveals that synaptic vesicle exocytosis and endocytosis are coupled by a single stochastic mode
Open accessAbstract
The nature of synaptic vesicle recycling at nerve terminals has been a subject of considerable debate for >35 years. Here, we report the use of an optical strategy that allows the exocytosis and retrieval of synaptic components to be tracked in real time at single-molecule sensitivity in living nerve terminals. This approach has allowed us to examine the recycling of synaptic vesicles in response to single action potentials. Our results show that, after exocytosis, individual synaptic vesicles are retrieved by a stochastic process with an exponential distribution of delay times, with a mean time of approximately 14 s. We propose that evidence for fast endocytosis, such as that proposed to support the presence of kiss-and-run, is likely explained by the stochastic nature of a slower process.
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vGpH increases in green fluorescence intensity upon vesicle fusion.
“vGpH, which increases in green fluorescence intensity upon vesicle fusion12.”
From A trans-synaptic nanocolumn aligns neurotransmitter release to receptors (2016) · cites this paper as [12]
When ultrafast endocytosis is blocked, a slow clathrin-mediated endocytic pathway can kick in.
“When ultrafast endocytosis is blocked, a slow clathrin-mediated endocytic pathway can kick in7 - this is consistent with observations from live-cell imaging of endocytosis68–70.”
From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [68]
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Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets
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Self-citationVesicular Monoamine and Glutamate Transporters Select Distinct Synaptic Vesicle Recycling Pathways
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- Authors
- Balaji, J., & Ryan, T. A.
- Affiliations
- Weill Cornell Medicine (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-12-18
- Volume
- 104
- Issue
- 51
- Pages
- 20576-20581
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2154473
- OpenAlex
- W2008643711
- Cited by
- 279
- References
- 24
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 11 · 2023: 7 · 2022: 18 · 2021: 12 · 2020: 14 · 2019: 17 · 2018: 18 · 2017: 19 · 2016: 12 · 2015: 14 · 2014: 23 · 2013: 20 · 2012: 10
- FWCI
- 7.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- University of California, San Francisco
- National Institute of Neurological Disorders and Stroke (R01NS036942)
- 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 recycling, exocytosis, endocytosis, kiss-and-run, single-vesicle imaging, single-molecule tracking, presynaptic terminals, synaptic transmission
- MeSH terms
- Animals, Cells, Cultured, Endocytosis, Exocytosis, Microscopy, Fluorescence, Synaptic Vesicles, Rats, Sprague-Dawley, Photobleaching, Green Fluorescent Proteins, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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