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Synaptic Vesicle Endocytosis
Open accessAbstract
Neurons can sustain high rates of synaptic transmission without exhausting their supply of synaptic vesicles. This property relies on a highly efficient local endocytic recycling of synaptic vesicle membranes, which can be reused for hundreds, possibly thousands, of exo-endocytic cycles. Morphological, physiological, molecular, and genetic studies over the last four decades have provided insight into the membrane traffic reactions that govern this recycling and its regulation. These studies have shown that synaptic vesicle endocytosis capitalizes on fundamental and general endocytic mechanisms but also involves neuron-specific adaptations of such mechanisms. Thus, investigations of these processes have advanced not only the field of synaptic transmission but also, more generally, the field of endocytosis. This article summarizes current information on synaptic vesicle endocytosis with an emphasis on the underlying molecular mechanisms and with a special focus on clathrin-mediated endocytosis, the predominant pathway of synaptic vesicle protein internalization.
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“Following exocytosis, synaptic vesicles are recovered through clathrin-mediated, ultrafast, bulk, or kiss-and-run endocytic pathways.”
From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [30]
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“Bulk endocytosis is triggered by intense or prolonged neuronal stimulation. This pathway involves the retrieval of large portions of the plasma membrane in the form of large endocytic vacuoles [30]. New SVs are subsequently regenerated from these larger structures through clathrin-mediated budding [12,31].”
From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [30]
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“Clathrin-mediated endocytosis (CME) is the most prevalent pathway for SV retrieval. It involves the formation of clathrin-coated pits that bud off from the plasma membrane, internalizing SV components within tens of seconds following full-collapse fusion [30,31].”
From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [30]
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“The process of exocytosis is responsible for the release of neurotransmitters, while the process of endocytosis is responsible for the recycling of the synaptic vesicle membranes [148].”
From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [148]
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“At the synapse, the release of neurotransmitters relies on the two fundamental biological events, such as exocytosis and endocytosis.”
From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [148]
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“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 [2]
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“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 [2]
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“Kiss-and-run is a rapid mechanism that involves a transient opening of a fusion pore, allowing for neurotransmitter release without full collapse of the SV into the plasma membrane [30]. The vesicle is then rapidly retrieved, often within approximately one second [31,32].”
From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [30]
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PI(4,5)P2 is a master regulator for Ca2+-triggered vesicle exocytosis
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Gross, J., Knipper, M., & Mazurek, B. (2024) · Biomedicines · doi:10.3390/biomedicines12071615 · Cited by 5
Various approaches for measurement of synaptic vesicle endocytosis at the central nerve terminal
Jin, Y., Seo, K. H., Ko, H. M., Jung, T. W., Chung, Y. H., Lee, J. H., Park, H. H., Kim, H., Jeong, J. H., & Lee, S. H. (2019) · Archives of Pharmacal Research · doi:10.1007/s12272-019-01161-w · Cited by 5
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STED Imaging of Vesicular Endocytosis in the Synapse
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Rate-limiting recovery processes in neurotransmission under sustained stimulation
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Unraveling protein–protein interactions in clathrin assemblies via atomic force spectroscopy
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Synaptic Vesicle Recycling Is Unaffected in the Ts65Dn Mouse Model of Down Syndrome
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Roles in physiology and disease of the inositol phosphatase synaptojanin 1
Camilli, P. V. D. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2025.159708 · Cited by 3
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Putting a brake on synaptic vesicle endocytosis
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Metadata
- Authors
- Saheki, Y., & De Camilli, P.
- Affiliations
- Howard Hughes Medical Institute (US)
- ORCID
- Saheki, Y.
- Venue
- Cold Spring Harbor Perspectives in Biology
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2012-07-03
- Volume
- 4
- Issue
- 9
- Pages
- a005645-a005645
- ISSN
- 1943-0264 (ISSN-L)
- PMC
- PMC3428771
- OpenAlex
- W2804806451
- Cited by
- 457
- References
- 297
- Citations by year
- 2026: 32 · 2025: 20 · 2024: 24 · 2023: 32 · 2022: 38 · 2021: 32 · 2020: 40 · 2019: 38 · 2018: 30 · 2017: 41 · 2016: 33 · 2015: 37 · 2014: 36 · 2013: 17 · 2012: 4
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Neurological Disorders and Stroke (R37NS036251)
- 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 endocytosis, synaptic vesicle recycling, clathrin-mediated endocytosis, synaptic transmission, membrane traffic, exocytosis
- MeSH terms
- Clathrin, Endocytosis, Exocytosis, Intracellular Membranes, Membrane Fusion, Actin Cytoskeleton, Models, Biological, Synaptic Transmission, Phosphatidylinositols, Synaptic Vesicles, Protein Transport, Clathrin-Coated Vesicles
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