Ultrastructure of the axonal periodic scaffold reveals a braid-like organization of actin rings
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Abstract
Recent super-resolution microscopy studies have unveiled a periodic scaffold of actin rings regularly spaced by spectrins under the plasma membrane of axons. However, ultrastructural details are unknown, limiting a molecular and mechanistic understanding of these enigmatic structures. Here, we combine platinum-replica electron and optical super-resolution microscopy to investigate the cortical cytoskeleton of axons at the ultrastructural level. Immunogold labeling and correlative super-resolution/electron microscopy allow us to unambiguously resolve actin rings as braids made of two long, intertwined actin filaments connected by a dense mesh of aligned spectrins. This molecular arrangement contrasts with the currently assumed model of actin rings made of short, capped actin filaments. Along the proximal axon, we resolved the presence of phospho-myosin light chain and the scaffold connection with microtubules via ankyrin G. We propose that braided rings explain the observed stability of the actin-spectrin scaffold and ultimately participate in preserving the axon integrity.
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Cell unroofing mechanically removes the dorsal surface of adherent cells, exposing the cytoplasmic face of the plasma membrane attached to a solid substrate.
“Cell unroofing mechanically removes the dorsal surface of adherent cells, thereby exposing the cytoplasmic face of the plasma membrane that remains attached to a solid substrate26,27.”
From Ghost Neuron preparation unlocks high-resolution structural mapping of intracellular architecture in axons (2026) · cites this paper as [26]
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Bodakuntla, S., Marelli, J., Vasquez-Montes, V., Glauser, S., Biertümpfel, C., & Mizuno, N. (2026) · Nature Communications · doi:10.1038/s41467-026-77741-4
- Authors
- Vassilopoulos, S., Gibaud, S., Jimenez, A., Caillol, G., & Leterrier, C.
- Affiliations
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Vassilopoulos, Stéphane
- Leterrier, Christophe
- Venue
- Nature Communications
- Published
- 2019-12-20
- Volume
- 10
- Issue
- 1
- Pages
- 5803-5803
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6925202
- OpenAlex
- W2995073429
- Cited by
- 143
- References
- 2
- Citations by year
- 2026: 9 · 2025: 19 · 2024: 20 · 2023: 13 · 2022: 23 · 2021: 29 · 2020: 25 · 2019: 5
- FWCI
- 10.77
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-14-CE12-0001)
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique
- Sorbonne Université
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- actin rings, spectrin, cortical cytoskeleton, axon ultrastructure, ankyrin-G, axon integrity, immunogold labeling
- MeSH terms
- Actins, Animals, Axons, Cell Membrane, Cells, Cultured, Embryo, Mammalian, Hippocampus, Microscopy, Electron, Microscopy, Fluorescence, Microtubules, Spectrin, Rats, Wistar, Ankyrins, Myosin Light Chains, Primary Cell Culture
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