A cryo-ET survey of microtubules and intracellular compartments in mammalian axons
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Abstract
The neuronal axon is packed with cytoskeletal filaments, membranes, and organelles, many of which move between the cell body and axon tip. Here, we used cryo-electron tomography to survey the internal components of mammalian sensory axons. We determined the polarity of the axonal microtubules (MTs) by combining subtomogram classification and visual inspection, finding MT plus and minus ends are structurally similar. Subtomogram averaging of globular densities in the MT lumen suggests they have a defined structure, which is surprising given they likely contain the disordered protein MAP6. We found the endoplasmic reticulum in axons is tethered to MTs through multiple short linkers. We surveyed membrane-bound cargos and describe unexpected internal features such as granules and broken membranes. In addition, we detected proteinaceous compartments, including numerous virus-like capsid particles. Our observations outline novel features of axonal cargos and MTs, providing a platform for identification of their constituents.
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Several studies have imaged neuronal processes by cryo-EM and cryo-ET, showing neurites are accessible to cryogenic imaging but persistent challenges remain at molecular resolution due to poor contrast and cytoplasmic denseness.
“Several studies have imaged neuronal processes by cryo-EM and cryo-ET19–25, showing that neurites are accessible to cryogenic imaging, while also revealing persistent challenges in obtaining information at a molecular resolution due to poor contrast and cytoplasmic denseness.”
From Ghost Neuron preparation unlocks high-resolution structural mapping of intracellular architecture in axons (2026) · cites this paper as [21]
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Highly accurate protein structure prediction with AlphaFold
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Autophagosomes initiate distally and mature during transport toward the cell soma in primary neurons
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BackgroundIn-cell architecture of an actively transcribing-translating expressome
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Cited by
Sorted by citations
Bodakuntla, S., Marelli, J., Vasquez-Montes, V., Glauser, S., Biertümpfel, C., & Mizuno, N. (2026) · Nature Communications · doi:10.1038/s41467-026-77741-4
- Authors
- Foster, H. E., Ventura Santos, C., & Carter, A. P.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- MRC Laboratory of Molecular Biology, Cambridge, UK
- Corresponding author
- Foster, Helen E.
- Carter, Andrew P.
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2021-12-08
- Volume
- 221
- Issue
- 2
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC7612188
- OpenAlex
- W4200159501
- Cited by
- 69
- References
- 6
- Citations by year
- 2026: 18 · 2025: 10 · 2024: 13 · 2023: 13 · 2022: 13 · 2021: 2
- FWCI
- 4.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (WT210711)
- Medical Research Council (MRC_UP_A025_1011)
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Keywords
- axonal microtubules, sensory axons, MAP6, intracellular transport
- MeSH terms
- Animals, Axons, Capsid, Cell Compartmentation, Cytoskeleton, Drosophila melanogaster, Endoplasmic Reticulum, Ganglia, Spinal, Mammals, Microtubules, Nerve Tissue Proteins, Tomography, Multivariate Analysis, Cryoelectron Microscopy, Intracellular Space
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