CryoET reveals actin filaments within platelet microtubules
Open accessPublished version of a preprint
Abstract
Crosstalk between the actin and microtubule cytoskeletons is important for many cellular processes. Recent studies have shown that microtubules and F-actin can assemble to form a composite structure where F-actin occupies the microtubule lumen. Whether these cytoskeletal hybrids exist in physiological settings and how they are formed is unclear. Here, we show that the short-crossover Class I actin filament previously identified inside microtubules in human HAP1 cells is cofilin-bound F-actin. Lumenal F-actin can be reconstituted in vitro, but cofilin is not essential. Moreover, actin filaments with both cofilin-bound and canonical morphologies reside within human platelet microtubules under physiological conditions. We propose that stress placed upon the microtubule network during motor-driven microtubule looping and sliding may facilitate the incorporation of actin into microtubules.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 [43]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 39
- [1]Dogterom, M. & Koenderink, G. H. Actin-microtubule crosstalk in cell biology. Nat. Rev. Mol. Cell Biol. 20, 38–54 (2019). 30323238 · DOI
- [2]Pimm, M. L. & Henty-Ridilla, J. L. New twists in actin-microtubule interactions. Mol. Biol. Cell 32, 211–217 (2021). 33507109 PMC8098829 · DOI
- [3]Ventura Santos, C., Rogers, S. L. & Carter, A. P. CryoET shows cofilactin filaments inside the microtubule lumen. EMBO Rep. 24, e57264 (2023). 37702953 PMC10626427 · DOI · Paper page
- [4]Paul, D. M. et al. In situ cryo-electron tomography reveals filamentous actin within the microtubule lumen. J. Cell Biol.219, e201911154 (2020). PMC7480112 32478855
- [5]Egelman, E. H., Francis, N. & DeRosier, D. J. F-actin is a helix with a random variable twist. Nature 298, 131–135 (1982). 7201078 · DOI
- [6]Hanson, J. Axial Period of Actin Filaments. Nature 213, 353–356 (1967). · DOI
- [7]Dominguez, R. & Holmes, K. C. Actin structure and function. Annu Rev. Biophys. 40, 169–186 (2011). 21314430 PMC3130349 · DOI · Paper page
- [8]Stokes, D. L. & DeRosier, D. J. The variable twist of actin and its modulation by actin-binding proteins. J. Cell Biol. 104, 1005–1017 (1987). 3558475 PMC2114449 · DOI
- [9]McGough, A., Pope, B., Chiu, W. & Weeds, A. Cofilin changes the twist of F-actin: implications for actin filament dynamics and cellular function. J. Cell Biol. 138, 771–781 (1997). 9265645 PMC2138052 · DOI
- [10]Huehn, A. et al. The actin filament twist changes abruptly at boundaries between bare and cofilin-decorated segments. J. Biol. Chem. 293, 5377–5383 (2018). 29463680 PMC5900768 · DOI
- [11]Kimmerlin, Q., Strassel, C., Eckly, A. & Lanza, F. The tubulin code in platelet biogenesis. Semin Cell Dev. Biol. 137, 63–73 (2023). 35148939 · DOI
- [12]Atherton, J., Stouffer, M., Francis, F. & Moores, C. A. Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography. J. Cell Sci.135, jcs.259234 (2022). PMC9016625 35383828
- [13]Randall, T. S. et al. A small-molecule activator of kinesin-1 drives remodeling of the microtubule network. Proc. Natl Acad. Sci. USA 114, 13738–13743 (2017). 29229862 PMC5748212 · DOI
- [14]Reynolds, M. J., Hachicho, C., Carl, A. G., Gong, R. & Alushin, G. M. Bending forces and nucleotide state jointly regulate F-actin structure. Nature 611, 380–386 (2022). 36289330 PMC9646526 · DOI
- [15]Galkin, V. E. et al. Remodeling of actin filaments by ADF/cofilin proteins. Proc. Natl Acad. Sci. USA 108, 20568–20572 (2011). 22158895 PMC3251117 · DOI
- [16]Essletzbichler, P. et al. Megabase-scale deletion using CRISPR/Cas9 to generate a fully haploid human cell line. Genome Res 24, 2059–2065 (2014). 25373145 PMC4248322 · DOI
- [17]Farina, F. et al. The centrosome is an actin-organizing centre. Nat. Cell Biol. 18, 65–75 (2016). 26655833 PMC4880044 · DOI
- [18]Jolly, A. L. et al. Kinesin-1 heavy chain mediates microtubule sliding to drive changes in cell shape. Proc. Natl Acad. Sci. USA 107, 12151–12156 (2010). 20566873 PMC2901438 · DOI
- [19]Bender, M. et al. Microtubule sliding drives proplatelet elongation and is dependent on cytoplasmic dynein. Blood 125, 860–868 (2015). 25411426 PMC4311231 · DOI
- [20]Diagouraga, B. et al. Motor-driven marginal band coiling promotes cell shape change during platelet activation. J. Cell Biol. 204, 177–185 (2014). 24421335 PMC3897189 · DOI
- [21]Sadoul, K. New explanations for old observations: marginal band coiling during platelet activation. J. Thromb. Haemost. 13, 333–346 (2015). 25510620 · DOI
- [22]Patel-Hett, S. et al. Visualization of microtubule growth in living platelets reveals a dynamic marginal band with multiple microtubules. Blood 111, 4605–4616 (2008). 18230754 PMC2343595 · DOI
- [23]Wang, R. et al. Electron cryotomography reveals ultrastructure alterations in platelets from patients with ovarian cancer. Proc. Natl Acad. Sci. USA 112, 14266–14271 (2015). 26578771 PMC4655568 · DOI
- [24]Xu, Z. & Afzelius, B. A. The substructure of marginal bundles in human blood platelets. J. Ultrastruct. Mol. Struct. Res 99, 244–253 (1988). 3143769 · DOI
- [25]Behnke, O. & Zelander, T. Filamentous substructure of microtubules of the marginal bundle of mammalian blood platelets. J. Ultrastruct. Res 19, 147–165 (1967). 6028173 · DOI
- [26]Chaaban, S. & Brouhard, G. J. A microtubule bestiary: structural diversity in tubulin polymers. Mol. Biol. Cell 28, 2924–2931 (2017). 29084910 PMC5662251 · DOI · Paper page
- [27]Tsuji, C. & Dodding, M. P. Lumenal components of cytoplasmic microtubules. Biochem Soc. Trans. 50, 1953–1962 (2022). 36524962 PMC9788383 · DOI
- [28]Kile, B. T. et al. Mutations in the cofilin partner Aip1/Wdr1 cause autoinflammatory disease and macrothrombocytopenia. Blood 110, 2371–2380 (2007). 17515402 PMC1988957 · DOI
- [29]Kauskot, A. et al. LIM kinase/cofilin dysregulation promotes macrothrombocytopenia in severe von Willebrand disease-type 2B. JCI Insight 1, e88643 (2016). 27734030 PMC5053155 · DOI
- [30]Ghalloussi, D., Dhenge, A. & Bergmeier, W. New insights into cytoskeletal remodeling during platelet production. J. Thromb. Haemost. 17, 1430–1439 (2019). 31220402 PMC6760864 · DOI
- [31]Hoffmann, P. C. et al. Electron cryo-tomography reveals the subcellular architecture of growing axons in human brain organoids. Elife10, e70269 (2021). PMC8547956 34698018
- [32]Foster, H. E., Ventura Santos, C. & Carter, A. P. A cryo-ET survey of microtubules and intracellular compartments in mammalian axons. J. Cell Biol.221, e202103154 (2022). PMC7612188 34878519
- [33]Ferreira, J. L. et al. Variable microtubule architecture in the malaria parasite. Nat. Commun. 14, 1216 (2023). 36869034 PMC9984467 · DOI · Paper page
- [34]Cyrklaff, M. et al. Cryoelectron tomography reveals periodic material at the inner side of subpellicular microtubules in apicomplexan parasites. J. Exp. Med 204, 1281–1287 (2007). 17562819 PMC2118598 · DOI
- [35]Zens, B. et al. Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural landscape of extracellular matrix. J. Cell Biol.223, e202309125 (2024). PMC10955043 38506714
- [36]Kremer, J. R., Mastronarde, D. N. & McIntosh, J. R. Computer visualization of three-dimensional image data using IMOD. J. Struct. Biol. 116, 71–76 (1996). 8742726 · DOI
- [37]van Heel, M. & Keegstra, W. IMAGIC: a fast, flexible and friendly image analysis software system. Ultramicroscopy 7, 113–129 (1981). · DOI
- [38]Goudswaard, L. J. et al. Alterations in platelet proteome signature and impaired platelet integrin alpha(IIb)beta(3) activation in patients with COVID-19. J. Thromb. Haemost. 21, 1307–1321 (2023). 36716966 PMC9883069 · DOI
- [39]Zheng, S. et al. AreTomo: an integrated software package for automated marker-free, motion-corrected cryo-electron tomographic alignment and reconstruction. J. Struct. Biol. X 6, 100068 (2022). 35601683 PMC9117686
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
- Tsuji, C., Bradshaw, M., Allen, M. F., Jackson, M. L., Mantell, J., Borucu, U., Poole, A. W., Verkade, P., Hers, I., Paul, D. M., & Dodding, M. P.
- Affiliations
- University of Bristol (GB)
- Corresponding author
- Hers, Ingeborg
- Paul, Danielle M.
- Dodding, Mark P.
- ORCID
- Venue
- Nature Communications
- Published
- 2024-07-16
- Volume
- 15
- Issue
- 1
- Pages
- 5967-5967
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC11252303
- OpenAlex
- W4400689616
- Cited by
- 5
- References
- 0
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1
- FWCI
- 1.06
- Type
- journal article
- Language
- en
- Update notices
- correction (2024-11-28)
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Explore Bristol Research (submittedVersion, cc-by)
- Funders
- RCUK | Biotechnology and Biological Sciences Research Council (BB/W005581/1, BB/X017176/1)
- Lister Institute of Preventive Medicine (N/A)
- Wellcome Trust (203959/Z/16/Z, 219472/Z/19/Z)
- British Heart Foundation (FS/20/5/34973, FS/4yPhD/F/20/34125, SP/F/21/150023, PG/21/10760, FS/14/18/3071, FS/IBSRF/23/25156)
- National Centre for the Replacement Refinement and Reduction of Animals in Research (N/A)
- 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 › Molecular Biology › Protein Structure and Dynamics
- Keywords
- cofilin, microtubule sliding, HAP1 cells
- MeSH terms
- Actins, Blood Platelets, Humans, Actin Cytoskeleton, Microtubules, Cryoelectron Microscopy, Actin Depolymerizing Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review