Cited by 69Advanced Electron Microscopy Techniques and ApplicationsMicrotubule and mitosis dynamicsCancer Treatment and Pharmacology

A cryo-ET survey of microtubules and intracellular compartments in mammalian axons

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Foster, Helen E., Ventura Santos, Camilla, Carter, Andrew P.·2022·Journal of Cell Biology

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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.”

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Cited by

Sorted by citations

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
Published
2021-12-08
Volume
221
Issue
2
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
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
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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