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Cited by 11Microtubule and mitosis dynamicsCellular Mechanics and InteractionsAdvanced Electron Microscopy Techniques and Applications

CryoET shows cofilactin filaments inside the microtubule lumen

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Ventura Santos, Camilla, Rogers, Stephen L, Carter, Andrew P·2023·The EMBO Reports
DOI 10.15252/embr.202357264PMC PMC10626427
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Abstract

Cytoplasmic microtubules are tubular polymers that can harbor small proteins or filaments inside their lumen. The identities of these objects and mechanisms for their accumulation have not been conclusively established. Here, we used cryogenic electron tomography of Drosophila S2 cell protrusions and found filaments inside the microtubule lumen, which resemble those reported recently in human HAP1 cells. The frequency of these filaments increased upon inhibition of the sarco/endoplasmic reticulum Ca 2+ ATPase with the small molecule drug thapsigargin. Subtomogram averaging showed that the luminal filaments adopt a helical structure reminiscent of cofilin‐bound actin (cofilactin). Consistent with this, we observed cofilin dephosphorylation, an activating modification, in cells under the same conditions that increased luminal filament occurrence. Furthermore, RNA interference knock‐down of cofilin reduced the frequency of luminal filaments with cofilactin morphology. These results suggest that cofilin activation stimulates its accumulation on actin filaments inside the microtubule lumen.

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  • Extensive decoration of cofilin on actin filaments is consistent with in situ cryo-ET studies that identified fully decorated cofilin-actin filaments at the growth cone of axons, within the lumen of microtubules in Drosophila S2 cells and platelets.

    “This extensive decoration of cofilin on actin filaments is consistent with in situ cryo-ET studies that identified fully decorated cofilin-actin filaments at the growth cone of axons42, within the lumen of microtubules in Drosophila S2 cells and platelets43,44.”

    From Ghost Neuron preparation unlocks high-resolution structural mapping of intracellular architecture in axons (2026) · cites this paper as [44]

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Cited by

Sorted by citations

Authors
Ventura Santos, C., Rogers, S. L., & Carter, A. P.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • MRC Laboratory of Molecular Biology (GB)
Corresponding author
Carter, Andrew P
ORCID
Venue
The EMBO Reports
Publisher
Springer Science and Business Media LLC
Published
2023-09-13
Volume
24
Issue
11
Pages
e57264-e57264
ISSN
  • 1469-221X (ISSN-L)
  • 1469-3178
DOI
10.15252/embr.202357264
PMC
PMC10626427
OpenAlex
W4386704679
Cited by
11
References
0
Citations by year
2026: 3 · 2025: 2 · 2024: 5 · 2023: 1
FWCI
1.54
Type
journal article
Language
en
Open access
Licence
Locations
  • EMBO Reports (publishedVersion, other-oa)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
Funders
  • Cambridge Trust
  • HHS | NIH | National Institute of Neurological Disorders and Stroke (R21NS125795)
  • UKRI | Medical Research Council (MC_UP_A025_1011)
  • Wellcome Trust (210711/Z/18/Z)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
Keywords
cofilin dephosphorylation, F-actin, thapsigargin, sarco/endoplasmic reticulum Ca2+-ATPase, Drosophila S2 cells, cell protrusions, subtomogram averaging

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