Synaptic Vesicle Endocytosis Occurs on Multiple Timescales and Is Mediated by Formin-Dependent Actin Assembly
Open accessAbstract
Neurotransmission is based on the exocytic fusion of synaptic vesicles (SVs) followed by endocytic membrane retrieval and the reformation of SVs. Recent data suggest that at physiological temperature SVs are internalized via clathrin-independent ultrafast endocytosis (UFE) within hundreds of milliseconds, while other studies have postulated a key role for clathrin-mediated endocytosis (CME) of SV proteins on a timescale of seconds to tens of seconds. Here we demonstrate using cultured hippocampal neurons as a model that at physiological temperature SV endocytosis occurs on several timescales from less than a second to several seconds, yet, is largely independent of clathrin. Clathrin-independent endocytosis (CIE) of SV membranes is mediated by actin-nucleating formins such as mDia1, which are required for the formation of presynaptic endosome-like vacuoles from which SVs reform. Our results resolve previous discrepancies in the field and suggest that SV membranes are predominantly retrieved via CIE mediated by formin-dependent actin assembly.
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Ultrafast 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 [8]
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 [8]
Recent work suggests that the actin nucleator formin is required for synaptic vesicle endocytosis at small hippocampal boutons.
“Additionally, recent work suggests that the actin nucleator formin is required for synaptic vesicle endocytosis at small hippocampal boutons8.”
From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [8]
Cites
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Actin Is Crucial for All Kinetically Distinguishable Forms of Endocytosis at Synapses
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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
“Additionally, recent work suggests that the actin nucleator formin is required for synaptic vesicle endocytosis at small hippocampal boutons 8 .”
Small, C., Harper, C., Jiang, A., Kontaxi, C., Pronot, M., Yak, N., Malapaka, A., Davenport, E. C., Wallis, T. P., Gormal, R. S., et al. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16186 · Cited by 14 · see citing works
- Authors
- Soykan, T., Kaempf, N., Sakaba, T., Vollweiter, D., Goerdeler, F., Puchkov, D., Kononenko, N. L., & Haucke, V.
- Affiliations
- Leibniz-Forschungsinstitut für Molekulare Pharmakologie (DE)
- Doshisha University (JP)
- University of Cologne (DE)
- Corresponding author
- Haucke, Volker
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 93
- Issue
- 4
- Pages
- 854-866.e4
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2590662729
- Cited by
- 178
- References
- 9
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 18 · 2023: 19 · 2022: 21 · 2021: 29 · 2020: 22 · 2019: 20 · 2018: 16 · 2017: 15
- FWCI
- 10.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (15H04261)
- NeuroCure Exzellenzcluster (Exc-257)
- Deutsche Forschungsgemeinschaft (/ HA2686/13-1, SFB958/A01)
- 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, clathrin-independent endocytosis, clathrin-mediated endocytosis, formins, mDia1, actin assembly, neurotransmission, hippocampal neurons
- MeSH terms
- Actins, Animals, Carrier Proteins, Clathrin, Endocytosis, Hippocampus, Mice, Transgenic, Synaptic Transmission, Endosomes, Synaptic Vesicles
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