Dynamin is primed at endocytic sites for ultrafast endocytosis
Open accessAbstract
Summary: Dynamin mediates fission of vesicles from the plasma membrane during endocytosis. Typically, dynamin is recruited from the cytosol to endocytic sites, requiring seconds to tens of seconds. However, ultrafast endocytosis in neurons internalizes vesicles as quickly as 50 ms during synaptic vesicle recycling. Here we demonstrate that Dynamin 1 is pre-recruited to endocytic sites for ultrafast endocytosis. Specifically, Dynamin 1xA, a splice variant of Dynamin 1, interacts with Syndapin 1 to form molecular condensates on the plasma membrane when the proline-rich domain of this variant is dephosphorylated. When this domain is mutated to include phosphomimetic residues or Syndapin 1’s dynamin-interacting domain is mutated, Dynamin 1xA becomes diffuse, and consequently, ultrafast endocytosis slows down by ∼100-fold. Mechanistically, Syndapin 1 acts as an adaptor by binding the plasma membrane and stores Dynamin 1xA at endocytic sites. This cache bypasses the recruitment step and accelerates endocytosis at synapses.
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Endocytic proteins such as Synaptojanin 1, Endophilin A, Syndapin 1, and Dynamin 1 can further curve the membrane and generate vesicles.
“Thereafter, endocytic proteins such as Synaptojanin 1, Endophilin A, Syndapin 1, and Dynamin 1 can further curve the membrane and generate vesicles47–50.”
From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [49]
The Summary (p. 1) says Dynamin mediates vesicle fission, and “The mode of endocytosis at synapses” (p. 12) says Dynamin 1, Endophilin A, and Synaptojanin 1 cinch the neck of an endocytic pit. But “Syndapin 1 recruits Dyn1xA to the plasma membrane” (p. 14) describes Syndapin 1 chiefly as an adaptor that tethers Dynamin 1, rather than establishing that it curves the membrane to generate vesicles. (LLM, conf=0.86)
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Research works printed but not linked: 12
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- Clayton, E.L., and Cousin, M.A. (2009). The molecular physiology of activity-dependent bulk endocytosis of synaptic vesicles. Journal of Neurochemistry 111, 901-914.
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- Dittman, J., and Ryan, T.A. (2009). Molecular Circuitry of Endocytosis at Nerve Terminals. Annual Review of Cell and Developmental Biology 25, 133-160.
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Cited by
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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
“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-citationSmall, 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
Self-citationSmall, C., Harper, C., Jiang, A., Kontaxi, C., Yak, N., Malapaka, A., Davenport, E. C., Wallis, T. P., Gormal, R. S., Joensuu, M., et al. (2022) · doi:10.1101/2022.12.12.520075 · Cited by 4 · see citing works
Self-citationSynaptic 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
“UFE and ADBE may also share the same molecular mechanism, although they were originally proposed to be triggered by mild and intense stimulation respectively (Blumrich et al. 2023; Clayton and Cousin 2009; Imoto et al. 2022, 2024; Smillie et al. 2005; Watanabe et al. 2018; Xue et al. 2011).”
Self-citation
- Authors
- Imoto, Y., Raychaudhuri, S., Fenske, P., Sandoval, E., Itoh, K., Blumrich, E.-M., Mamer, L., Zarebidaki, F., Söhl-Kielczynski, B., Trimbuch, T., Nayak, S., Iwasa, J. H., Jorgensen, E. M., Cousin, M. A., Rosenmund, C., & Watanabe, S.
- Affiliations
- Johns Hopkins University (US)
- Charité – Universitätsmedizin Berlin (DE)
- Simons Initiative for the Developing Brain (GB)
- University of Utah (US)
- Corresponding author
- Imoto, Yuuta
- Rosenmund, Christian
- Watanabe, Shigeki
- ORCID
- Venue
- Neuron
- Publisher
- openRxiv
- Published
- 2021-02-16
- Volume
- 110
- Issue
- 17
- Pages
- 2815-2835.e13
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC9464723
- OpenAlex
- W4284973934
- Cited by
- 109
- References
- 0
- Citations by year
- 2026: 12 · 2025: 32 · 2024: 26 · 2023: 28 · 2022: 11
- FWCI
- 12.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuron (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation (1727260)
- Howard Hughes Medical Institute (NSF 2148534)
- McKnight Endowment Fund for Neuroscience
- Alfred P. Sloan Foundation
- National Sleep Foundation
- McKnight Foundation
- Johns Hopkins University
- Wellcome Trust (204954/Z/16/Z)
- Deutsche Forschungsgemeinschaft
- National Institutes of Health (Exc257, CRG958/A5, 1dp2ns111133-01, NS034307)
- Japan Society for the Promotion of Science
- National Institute of Neurological Disorders and Stroke (R37NS034307, DP2 NS111133, NS034307, R01NS034307, R01NS105810, 1DP2 NS111133-01)
- 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 › Cell Biology › Caveolin-1 and cellular processes
- Keywords
- dynamin 1, synaptic vesicle recycling, liquid-like condensates, adaptor proteins, plasma membrane, single-particle tracking
- MeSH terms
- Endocytosis, Nerve Tissue Proteins, Synaptic Vesicles, Dynamins, Dynamin I
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