Axon initial segment cytoskeleton comprises a multiprotein submembranous coat containing sparse actin filaments
Open accessAbstract
The axon initial segment (AIS) of differentiated neurons regulates action potential initiation and axon–dendritic polarity. The latter function depends on actin dynamics, but actin structure and functions at the AIS remain unclear. Using platinum replica electron microscopy (PREM), we have characterized the architecture of the AIS cytoskeleton in mature and developing hippocampal neurons. The AIS cytoskeleton assembly begins with bundling of microtubules and culminates in formation of a dense, fibrillar–globular coat over microtubule bundles. Immunogold PREM revealed that the coat contains a network of known AIS proteins, including ankyrin G, spectrin βIV, neurofascin, neuronal cell adhesion molecule, voltage-gated sodium channels, and actin filaments. Contrary to existing models, we find neither polarized actin arrays, nor dense actin meshworks in the AIS. Instead, the AIS contains two populations of sparse actin filaments: short, stable filaments and slightly longer dynamic filaments. We propose that stable actin filaments play a structural role for formation of the AIS diffusion barrier, whereas dynamic actin may promote AIS coat remodeling.
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Surfactant-based extraction methods have provided access to cytoskeletal organization, including neuronal processes.
“Related surfactant-based extraction methods have provided informative access to cytoskeletal organization, including neuronal processes30–32.”
From Ghost Neuron preparation unlocks high-resolution structural mapping of intracellular architecture in axons (2026) · cites this paper as [31]
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- Authors
- Jones, S. L., Korobova, F., & Svitkina, T.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Svitkina, Tatyana
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2014-04-07
- Volume
- 205
- Issue
- 1
- Pages
- 67-81
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC3987141
- OpenAlex
- W2165073216
- Cited by
- 111
- References
- 55
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 8 · 2020: 11 · 2019: 14 · 2018: 8 · 2017: 14 · 2016: 15 · 2015: 14 · 2014: 6
- FWCI
- 6.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM070898, GM-070898, R01GM095977, GM095977)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-007516, T32HD007516)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- axon initial segment, cytoskeleton, F-actin, microtubule bundling, ankyrin-G, neurofascin, neuronal cell adhesion molecule, voltage-gated sodium channels, action potential generation, diffusion barrier, hippocampal neurons, actin dynamics
- MeSH terms
- Actins, Animals, Axons, Cells, Cultured, Hippocampus, Immunohistochemistry, Actin Cytoskeleton, Microscopy, Electron, Nerve Tissue Proteins, Time Factors, Cell Polarity, Rats, Sprague-Dawley, Bridged Bicyclo Compounds, Heterocyclic, Thiazolidines, Neurogenesis
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