UNC-45A Breaks MT Lattice Independent of its Effect on Non-Muscle Myosin II
Open accessPublished version of a preprint
Abstract
In invertebrates, UNC-45 regulates myosin stability and functions. Vertebrates have two distinct isoforms of the protein: UNC-45B, expressed in muscle cells only and UNC-45A, expressed in all cells and implicated in regulating both Non-Muscle Myosin II (NMII)- and microtubule (MT)-associated functions. Here we show that both, in vitro and in cells, UNC-45A binds to the MT lattice leading to MT bending, breakage and depolymerization. Furthermore, we show that UNC-45A destabilizes MTs independent of its NMII C-terminal binding domain and even in presence of the NMII inhibitor blebbistatin. These findings identified UNC-45A as a novel type of MT-severing protein with a not mutually exclusive but rather dual role in regulating NMII activity and MT stability. Because many human diseases, from cancer to neurodegenerative diseases, are caused by or associated with deregulation of MT stability our findings have profound implications in both, the biology of MTs as well as the biology of human diseases and possible therapeutic implications for their treatment.
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?
The chaperone UNC45a binds curved, but not straight, microtubules.
“a recent study has suggested that the chaperone UNC45a binds curved, but not straight, microtubules [41]”
From Paclitaxel induces <scp>NM2</scp> ‐dependent cellular contraction through <scp>GEF</scp> ‐ <scp>H1</scp> dissociation from microtubules and <scp>RhoA</scp> / <scp>ROCK</scp> activation in cancer cells (2026) · cites this paper as [41]
The Results section ('In vitro, UNC-45A-mediated MT destabilization…'; page unavailable) reports that UNC-45A binds robustly along microtubules and that microtubules develop kinks in its presence. It does not establish that UNC-45A binds curved microtubules selectively or fails to bind straight ones. (LLM, conf=0.86)
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
An Essential Role for Katanin in Severing Microtubules in the Neuron
Ahmad, F. J., Yu, W., McNally, F. J., & Baas, P. W. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.2.305 · Cited by 253 · see citing works
Baas, P. W., & Qiang, L. (2019) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.02.007 · Cited by 123 · see citing works
Flagged first, then by citations
Research works printed but not linked: 9
- Bailey, M. E., Jiang, N., Dima, R. I., and Ross, J. L. (2016). Invited review: Microtubule severing enzymes couple atpase activity with tubulin GTPase spring loading. Biopolymers 105, 547-556.
- Barral, J. M., Hutagalung, A. H., Brinker, A., Hartl, F. U., and Epstein, H. F. (2002). Role of the myosin assembly protein UNC-45 as a molecular chaperone for myosin. Science 295, 669-671. (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
- Fabris, L., Berton, S., Pellizzari, I., Segatto, I., D'Andrea, S., Armenia, J., Bomben, R., Schiappacassi, M., Gattei, V., Philips, M. R., et al. (2015). p27kip1 controls H-Ras/MAPK activation and cell cycle entry via modulation of MT stability. Proceedings of the National Academy of Sciences of the United States of America 112, 13916-13921.
- Godin, J. D., Thomas, N., Laguesse, S., Malinouskaya, L., Close, P., Malaise, O., Purnelle, A., Raineteau, O., Campbell, K., Fero, M., et al. (2012). p27(Kip1) is a microtubule-associated (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. protein that promotes microtubule polymerization during neuron migration. Developmental cell 23, 729-744.
- Hertzer, K. M., Ems-McClung, S. C., Kline-Smith, S. L., Lipkin, T. G., Gilbert, S. P., and Walczak, C. E. (2006). Full-length dimeric MCAK is a more efficient microtubule depolymerase than minimal domain monomeric MCAK. Mol Biol Cell 17, 700-710. (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
- Iizuka, Y., Cichocki, F., Sieben, A., Sforza, F., Karim, R., Coughlin, K., Isaksson Vogel, R., Gavioli, R., McCullar, V., Lenvik, T., et al. (2015). UNC-45A Is a Nonmuscle Myosin IIA Chaperone Required for NK Cell Cytotoxicity via Control of Lytic Granule Secretion. Journal of immunology 195, 4760-4770.
- which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
- Serres, M. P., Kossatz, U., Chi, Y., Roberts, J. M., Malek, N. P., and Besson, A. (2012). p27(Kip1) controls cytokinesis via the regulation of citron kinase activation. The Journal of clinical investigation 122, 844-858.
- Sharp, D. J., and Ross, J. L. (2012). Microtubule-severing enzymes at the cutting edge. Journal of cell science 125, 2561-2569.
Cited by
Sorted by citations
Asensio‐Juárez, G., Pérez‐Díaz, R., Ramos‐Solano, H., Garrido‐Casado, M., Talayero, V. C., & Vicente‐Manzanares, M. (2026) · Molecular Oncology · doi:10.1002/1878-0261.70333
- Authors
- Habicht, J., Mooneyham, A., Hoshino, A., Shetty, M., Zhang, X., Emmings, E., Yang, Q., Coombes, C., Gardner, M. K., & Bazzaro, M.
- Affiliations
- University of Minnesota (US)
- Medizinische Hochschule Brandenburg Theodor Fontane (DE)
- Corresponding author
- Bazzaro, Martina
- ORCID
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2020-01-01
- Volume
- 134
- Issue
- 1
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- PMC
- PMC7803465
- OpenAlex
- W3107501012
- Cited by
- 15
- References
- 2
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 1
- FWCI
- 1.11
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Journal of Cell Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ovarian Cancer Academy (OC160377)
- Randy Shaver Cancer Research and Community Fund (4)
- National Institute of General Medical Sciences (R01-GM130800, R35-GM126974)
- 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 › Heat shock proteins research
- Keywords
- non-muscle myosin II, microtubule lattice, microtubule severing, microtubule stability, microtubule depolymerization, microtubule bending, blebbistatin
- MeSH terms
- Animals, Humans, Microtubules, Myosins, Molecular Chaperones, Myosin Type II, Intracellular Signaling Peptides and Proteins, Rats
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
