HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions
Open accessAbstract
Genetic or pharmacological alteration of the activity of the histone deacetylase 6 (HDAC6) induces a parallel alteration in cell migration. Using tubacin to block deacetylation of α-tubulin, and not other HDAC6 substrates, yielded a motility reduction equivalent to agents that block all NAD-independent HDACs. Accordingly, we investigated how the failure to deacetylate tubulin contributes to decreased motility in HDAC6-inhibited cells. Testing the hypothesis that motility is reduced because cellular adhesion is altered, we found that inhibiting HDAC6 activity towards tubulin rapidly increased total adhesion area. Next, we investigated the mechanism of the adhesion area increase. Formation of adhesions proceeded normally and cell spreading was more rapid in the absence of active HDAC6; however, photobleaching assays and adhesion breakdown showed that adhesion turnover was slower. To test the role of hyperacetylated tubulin in altering adhesion turnover, we measured microtubule dynamics in HDAC6-inhibited cells because dynamic microtubules are required to target adhesions for turnover. HDAC6 inhibition yielded a decrease in microtubule dynamics that was sufficient to decrease focal adhesion turnover. Thus, our results suggest a scenario in which the decreased dynamics of hyperacetylated microtubules in HDAC6-inhibited cells compromises their capacity to mediate the focal adhesion dynamics required for rapid cell migration.
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Treatment with the HDAC6 inhibitor tubacin and genetic depletion of HDAC6 both increased focal adhesion assembly.
“Consistent with this, treatment with the HDAC6 inhibitor tubacin and genetic depletion of HDAC6 both increased focal adhesion assembly, in agreement with previous reports ([36], and this report).”
Cites
HDAC6 is a microtubule-associated deacetylase
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Self-citationHDAC6 Regulates Hsp90 Acetylation and Chaperone-Dependent Activation of Glucocorticoid Receptor
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HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo
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Self-citationAdhikari, N., Jha, T., & Ghosh, B. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01676 · Cited by 74 · see citing works
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- Authors
- Tran, A. D.-A., Marmo, T. P., Salam, A. A., Che, S., Finkelstein, E., Kabarriti, R., Xenias, H. S., Mazitschek, R., Hubbert, C., Kawaguchi, Y., Sheetz, M. P., Yao, T.-P., & Bulinski, J. C.
- Affiliations
- Columbia University (US)
- Broad Institute (US)
- Duke Medical Center (US)
- Department of Biological Sciences, Columbia University, New York, NY 10027, USA
- ORCID
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2007-04-15
- Volume
- 120
- Issue
- 8
- Pages
- 1469-1479
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2117298794
- Cited by
- 281
- References
- 6
- Citations by year
- 2026: 9 · 2025: 3 · 2024: 6 · 2023: 13 · 2022: 7 · 2021: 9 · 2020: 11 · 2019: 14 · 2018: 9 · 2017: 21 · 2016: 16 · 2015: 14 · 2014: 23 · 2013: 24 · 2012: 24
- FWCI
- 7.65
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion, cc-by)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS054022)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- 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
- Keywords
- HDAC6, tubulin deacetylation, alpha-tubulin acetylation, focal adhesions, cell migration, microtubule dynamics, cell spreading, tubacin, histone deacetylase
- MeSH terms
- Histone Deacetylase 6, Acetylation, Animals, Cell Adhesion, Cell Movement, Chlorocebus aethiops, Histone Deacetylases, Humans, Tubulin, COS Cells
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