Fast, Temperature-Sensitive and Clathrin-Independent Endocytosis at Central Synapses
Open accessAbstract
The fusion of neurotransmitter-filled vesicles during synaptic transmission is balanced by endocytotic membrane retrieval. Despite extensive research, the speed and mechanisms of synaptic vesicle endocytosis have remained controversial. Here, we establish low-noise time-resolved membrane capacitance measurements that allow monitoring changes in surface membrane area elicited by single action potentials and stronger stimuli with high-temporal resolution at physiological temperature in individual bona-fide mature central synapses. We show that single action potentials trigger very rapid endocytosis, retrieving presynaptic membrane with a time constant of 470 ms. This fast endocytosis is independent of clathrin but mediated by dynamin and actin. In contrast, stronger stimuli evoke a slower mode of endocytosis that is clathrin, dynamin, and actin dependent. Furthermore, the speed of endocytosis is highly temperature dependent with a Q10 of ∼3.5. These results demonstrate that distinct molecular modes of endocytosis with markedly different kinetics operate at central synapses.
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Synaptic vesicle endocytosis at mammalian central synapses is mediated by clathrin-independent ultrafast endocytosis.
“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 [9]
The Results section reports rapid, clathrin-independent endocytosis after single action potentials at mature central synapses. But the Abstract and Results also report a slower, clathrin-dependent mode after stronger stimuli, so the unqualified claim that synaptic vesicle endocytosis is mediated by the clathrin-independent mode overstates the finding. Our copy provides section labels but no page numbers for these passages. (LLM, conf=0.88)
Experimental — accuracy not yet measuredUltrafast endocytosis is tightly coupled to exocytosis in time and space.
“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 [9]
The Abstract reports that single action potentials trigger clathrin-independent endocytosis with a 470-ms time constant at mature central synapses, supporting rapid temporal coupling to exocytosis. The cited passages do not establish that endocytosis occurs close to exocytosis sites; the Discussion’s reference to a spatiotemporal calcium signal concerns regulation of endocytosis speed, not spatial coupling of the two processes. (LLM, conf=0.86)
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Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis
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- Authors
- Delvendahl, I., Vyleta, N. P., von Gersdorff, H., & Hallermann, S.
- Affiliations
- Leipzig University (DE)
- Oregon Health & Science University (US)
- Corresponding author
- Delvendahl, Igor
- Hallermann, Stefan
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 90
- Issue
- 3
- Pages
- 492-498
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC5125781
- OpenAlex
- W2339057475
- Cited by
- 141
- References
- 3
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 14 · 2023: 14 · 2022: 21 · 2021: 9 · 2020: 13 · 2019: 13 · 2018: 16 · 2017: 19 · 2016: 6
- FWCI
- 12.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- National Institute on Deafness and Other Communication Disorders (R01DC012938)
- 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 › Ion Transport and Channel Regulation
- Keywords
- synaptic vesicle endocytosis, clathrin-independent endocytosis, dynamin, actin, temperature dependence, membrane capacitance, neurotransmitter release, central synapses, Q10
- MeSH terms
- Action Potentials, Animals, Clathrin, Endocytosis, Estriol, Hippocampus, Mice, Inbred C57BL, Synaptic Transmission, Temperature, Time Factors, Rats
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