The Synaptic Vesicle Cycle Revisited: New Insights into the Modes and Mechanisms
Open accessAbstract
Neurotransmission is sustained by endocytosis and refilling of synaptic vesicles (SVs) locally within the presynapse. Until recently, a consensus formed that after exocytosis, SVs are recovered by either fusion pore closure (kiss-and-run) or clathrin-mediated endocytosis directly from the plasma membrane. However, recent data have revealed that SV formation is more complex than previously envisaged. For example, two additional recycling pathways have been discovered, ultrafast endocytosis and activity-dependent bulk endocytosis, in which SVs are regenerated from the internalized membrane and synaptic endosomes. Furthermore, these diverse modes of endocytosis appear to influence both the molecular composition and subsequent physiological role of individual SVs. In addition, previously unknown complexity in SV refilling and reclustering has been revealed. This review presents a modern view of the SV life cycle and discusses how neuronal subtype, physiological temperature, and individual activity patterns can recruit different endocytic modes to generate new SVs and sculpt subsequent presynaptic performance.
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Ultrafast bulk endocytosis and activity-dependent bulk endocytosis are also responsible for recycling of vesicles.
“Apart from those mechanisms, several other mechanisms, such as ultrafast bulk endocytosis and activity-dependent bulk endocytosis, are also responsible for the recycling of the vesicles [150,151].”
From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [151]
Clathrin-mediated endocytosis participates in synaptic vesicle recycling.
“The clathrin-mediated endocytosis participates in SV recycling [151].”
From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [151]
Endocytosis after exocytosis maintains a sufficient number of synaptic vesicles at presynapses.
“After exocytosis, vesicle membrane must be retrieved from the plasma membrane through endocytosis to keep the area of the plasma membrane constant and maintain a sufficient number of synaptic vesicles at presynapses1–4.”
From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [1]
After exocytosis, vesicle membrane must be retrieved from the plasma membrane through endocytosis to keep the area of the plasma membrane constant.
“After exocytosis, vesicle membrane must be retrieved from the plasma membrane through endocytosis to keep the area of the plasma membrane constant and maintain a sufficient number of synaptic vesicles at presynapses1–4.”
From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [1]
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Cites
Molecular anatomy of a trafficking organelle
Takamori, S., Holt, M., Stenius, K., Lemke, E. A., Grønborg, M., Riedel, D., Urlaub, H., Schenck, S., Brügger, B., Ringler, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.10.030 · Cited by 2,373 · see citing works
Ultrafast endocytosis at mouse hippocampal synapses
Watanabe, S., Rost, B. R., Camacho-Pérez, M., Davis, M. W., Söhl-Kielczynski, B., Rosenmund, C., & Jorgensen, E. M. (2013) · Nature · doi:10.1038/nature12809 · Cited by 607 · see citing works
Self-citationThe mechanisms and functions of spontaneous neurotransmitter release
Kavalali, E. T. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3875 · Cited by 486 · see citing works
Saheki, Y., & De Camilli, P. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005645 · Cited by 457 · see citing works
Release probability of hippocampal glutamatergic terminals scales with the size of the active zone
Holderith, N., Lorincz, A., Katona, G., Rózsa, B., Kulik, A., Watanabe, M., & Nusser, Z. (2012) · Nature Neuroscience · doi:10.1038/nn.3137 · Cited by 405 · see citing works
Clathrin regenerates synaptic vesicles from endosomes
Watanabe, S., Trimbuch, T., Camacho-Pérez, M., Rost, B. R., Brokowski, B., Söhl-Kielczynski, B., Felies, A., Davis, M. W., Rosenmund, C., & Jorgensen, E. M. (2014) · Nature · doi:10.1038/nature13846 · Cited by 333 · see citing works
Self-citationBalaji, J., & Ryan, T. A. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707574105 · Cited by 279 · see citing works
Identification of a mutation in synapsin I, a synaptic vesicle protein, in a family with epilepsy
Garcia, C. C., Blair, H. J., Seager, M., Coulthard, A., Tennant, S., Buddles, M., Curtis, A., & Goodship, J. A. (2004) · Journal of Medical Genetics · doi:10.1136/jmg.2003.013680 · Cited by 205 · see citing works
Dynamin I phosphorylation by GSK3 controls activity-dependent bulk endocytosis of synaptic vesicles
Clayton, E. L., Sue, N., Smillie, K. J., O'Leary, T., Bache, N., Cheung, G., Cole, A. R., Wyllie, D. J., Sutherland, C., Robinson, P. J., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2571 · Cited by 169 · see citing works
Self-citationActin Is Crucial for All Kinetically Distinguishable Forms of Endocytosis at Synapses
Wu, X.-S., Lee, S. H., Sheng, J., Zhang, Z., Zhao, W.-D., Wang, D., Jin, Y., Charnay, P., Ervasti, J. M., & Wu, L.-G. (2016) · Neuron · doi:10.1016/j.neuron.2016.10.014 · Cited by 109 · see citing works
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Research works printed but not linked: 1
- Farsi Z, Jahn R, Woehler A (2017) Proton electrochemical gradient: driving and regulating neurotransmitter uptake. Bioessays. Advance online pub- lication. Retrieved April 6, 2017. doi: 10.1002/bies.201600240. · DOI
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Guerrini, R., Conti, V., Mantegazza, M., Balestrini, S., Galanopoulou, A. S., & Benfenati, F. (2023) · Physiological Reviews · doi:10.1152/physrev.00063.2021 · Cited by 196 · see citing works
Brain cell type-specific cholesterol metabolism and implications for learning and memory
Li, D., Zhang, J., & Liu, Q. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.01.002 · Cited by 163 · see citing works
Brain high-throughput multi-omics data reveal molecular heterogeneity in Alzheimer’s disease
Eteleeb, A. M., Novotny, B. C., Tarraga, C. S., Sohn, C., Dhungel, E., Brase, L., Nallapu, A., Buss, J., Farias, F., Bergmann, K., et al. (2024) · PLOS Biology · doi:10.1371/journal.pbio.3002607 · Cited by 64 · see citing works
Insights of Endocytosis Signaling in Health and Disease
Pathak, C., Vaidya, F. U., Waghela, B. N., Jaiswara, P. K., Gupta, V. K., Kumar, A., Rajendran, B. K., & Ranjan, K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032971 · Cited by 59 · see citing works
Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis
Ogunmowo, T. H., Jing, H., Raychaudhuri, S., Kusick, G. F., Imoto, Y., Li, S., Itoh, K., Ma, Y., Jafri, H., Dalva, M. B., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38595-2 · Cited by 51 · see citing works
“We recently discovered that a splice variant of Dyna-min 1, Dyn1xA, forms condensates with Syndapin1 17 and pre-accumulates at the ‘ endocytic zone ’ where ultrafast endocytosis takes place, located immediately next to the active zone (within 100nm of the active zone edge) 18 .”
Self-citationcAMP-Dependent Synaptic Plasticity at the Hippocampal Mossy Fiber Terminal
Shahoha, M., Cohen, R., Ben-Simon, Y., & Ashery, U. (2022) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2022.861215 · Cited by 46 · see citing works
Vitet, H., Bruyère, J., Xu, H., Séris, C., Brocard, J., Abada, Y.-S., Delatour, B., Scaramuzzino, C., Venance, L., & Saudou, F. (2023) · eLife · doi:10.7554/elife.81011 · Cited by 13 · see citing works
Synaptic Vesicle Recycling at the Developing Presynapse
Kim, N., & Cousin, M. A. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70206 · Cited by 2 · see citing works
“As stated in the introduction, various modes of endocytosis are proposed to coexist at the presynapse, namely CME, ADBE and UFE.”
InfluentialSelf-citation
- Authors
- Chanaday, N. L., Cousin, M. A., Milosevic, I., Watanabe, S., & Morgan, J. R.
- Affiliations
- University of Edinburgh (GB)
- Johns Hopkins University (US)
- Marine Biological Laboratory (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2019-10-16
- Volume
- 39
- Issue
- 42
- Pages
- 8209-8216
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6794917
- OpenAlex
- W2980728936
- Cited by
- 255
- References
- 10
- Citations by year
- 2026: 28 · 2025: 57 · 2024: 36 · 2023: 33 · 2022: 38 · 2021: 33 · 2020: 29 · 2018: 1
- FWCI
- 2.90
- 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)
- Open Access Server of the Woods Hole Scientific Community (Woods Hole Scientific Community) (submittedVersion, cc-by-nc-nd)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- National Science Foundation (1727260)
- Alfred P. Sloan Foundation
- McKnight Foundation
- Wellcome Trust (204954/Z/16/Z)
- Deutsche Forschungsgemeinschaft (MI-1702/1)
- National Institutes of Health (1dp2ns111133-01, MH066198)
- National Institute on Aging
- National Institute of Mental Health (R01MH066198, MH-066198)
- National Institute of Neurological Disorders and Stroke (DP2 NS111133, R01NS105810, R01NS078165)
- 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, synaptic vesicle endocytosis, kiss-and-run, clathrin-mediated endocytosis, presynaptic terminals, neurotransmission
- MeSH terms
- Animals, Cell Membrane, Endocytosis, Humans, Synaptic Transmission, Neurons, Endosomes, Synapses, Synaptic Vesicles
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