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Clathrin regenerates synaptic vesicles from endosomes
Open accessAbstract
Ultrafast endocytosis can retrieve a single, large endocytic vesicle as fast as 50-100 ms after synaptic vesicle fusion. However, the fate of the large endocytic vesicles is not known. Here we demonstrate that these vesicles transition to a synaptic endosome about one second after stimulation. The endosome is resolved into coated vesicles after 3 s, which in turn become small-diameter synaptic vesicles 5-6 s after stimulation. We disrupted clathrin function using RNA interference (RNAi) and found that clathrin is not required for ultrafast endocytosis but is required to generate synaptic vesicles from the endosome. Ultrafast endocytosis fails when actin polymerization is disrupted, or when neurons are stimulated at room temperature instead of physiological temperature. In the absence of ultrafast endocytosis, synaptic vesicles are retrieved directly from the plasma membrane by clathrin-mediated endocytosis. These results may explain discrepancies among published experiments concerning the role of clathrin in synaptic vesicle endocytosis.
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“Indeed, ultrafast endocytosis initiates as fast as 20–50 ms after exocytosis and completes within 100 ms5–7.”
From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [7]
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“In this pathway, endocytic invaginations always form at the edge of the active zone5–7.”
From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [7]
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“Based on the reliance of ultrafast endocytosis on F-actin7 and the high sensitivity of actin polymerization to temperature change74–76, we attribute this result to a slowed actin turnover at the room temperature7.”
From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [7]
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“Several recent studies suggest that synaptic vesicle endocytosis is mediated by clathrin-independent ultrafast endocytosis at mammalian central synapses and is tightly coupled to exocytosis in time and space5–9.”
From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [7]
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“Several recent studies suggest that synaptic vesicle endocytosis is mediated by clathrin-independent ultrafast endocytosis at mammalian central synapses and is tightly coupled to exocytosis in time and space5–9.”
From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [7]
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“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 [7]
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“In our previous study, we demonstrated that ultrafast endocytosis fails when neurons are incubated at room temperature for 5 min prior to experiments – this failure is compensated by clathrin-mediated endocytosis7.”
From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [7]
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“When ultrafast endocytosis is blocked, clathrin-mediated endocytosis takes its place7.”
From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [7]
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Metadata
- Authors
- 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.
- Affiliations
- Howard Hughes Medical Institute (US)
- Charité – Universitätsmedizin Berlin (DE)
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Rosenmund, Christian
- Venue
- Nature
- Published
- 2014-10-08
- Volume
- 515
- Issue
- 7526
- Pages
- 228-233
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4291189
- OpenAlex
- W2029980283
- Cited by
- 333
- References
- 49
- Citations by year
- 2026: 17 · 2025: 30 · 2024: 29 · 2023: 26 · 2022: 33 · 2021: 26 · 2020: 32 · 2019: 29 · 2018: 20 · 2017: 33 · 2016: 22 · 2015: 29 · 2014: 7
- FWCI
- 15.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Neurological Disorders and Stroke (R37NS034307, NS034307, R01NS034307)
- 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
- clathrin, synaptic vesicle recycling, coated vesicles, clathrin-mediated endocytosis, actin polymerization, temperature dependence, optogenetic stimulation, high-pressure freezing, axon terminals, synaptic vesicle fusion
- MeSH terms
- Animals, Cell Membrane, Clathrin, Endocytosis, Humans, Endosomes, Synaptic Vesicles, Temperature, Mice
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