Lymphocyte Chemotaxis Is Regulated by Histone Deacetylase 6, Independently of Its Deacetylase Activity
Open accessAbstract
In this work, the role of HDAC6, a type II histone deacetylase with tubulin deacetylase activity, in lymphocyte polarity, motility, and transmigration was explored. HDAC6 was localized at dynamic subcellular structures as leading lamellipodia and the uropod in migrating T-cells. However, HDAC6 activity did not appear to be involved in the polarity of migrating lymphocytes. Overexpression of HDAC6 in freshly isolated lymphocytes and T-cell lines increased the lymphocyte migration mediated by chemokines and their transendothelial migration under shear flow. Accordingly, the knockdown of HDAC6 expression in T-cells diminished their chemotactic capability. Additional experiments with HDAC6 inhibitors (trichostatin, tubacin), other structural related molecules (niltubacin, MAZ-1391), and HDAC6 dead mutants showed that the deacetylase activity of HDAC6 was not involved in the modulatory effect of this molecule on cell migration. Our results indicate that HDAC6 has an important role in the chemotaxis of T-lymphocytes, which is independent of its tubulin deacetylase activity.
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HDAC6 has catalytic-dependent and -independent functions.
“In addition, we showed that HDAC6 has catalytic‐dependent and ‐independent functions [68].”
Cites
HDAC6 is a microtubule-associated deacetylase
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HDAC6 Regulates Hsp90 Acetylation and Chaperone-Dependent Activation of Glucocorticoid Receptor
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Self-citationHDAC-6 interacts with and deacetylates tubulin and microtubules in vivo
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Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders
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Self-citation
- Authors
- Cabrero, J. R., Serrador, J. M., Barreiro, O., Mittelbrunn, M., Naranjo-Suárez, S., Martín-Cófreces, N., Vicente-Manzanares, M., Mazitschek, R., Bradner, J. E., Ávila, J., Valenzuela-Fernández, A., & Sánchez-Madrid, F.
- Affiliations
- *Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain;
- Universitat de València (ES)
- Hospital Universitario de La Princesa (ES)
- Broad Institute (US)
- Consejo Superior de Investigaciones Científicas (ES)
- Venue
- Molecular Biology of the Cell
- Published
- 2006-08
- Volume
- 17
- Issue
- 8
- Pages
- 3435-3445
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- OpenAlex
- W2146671895
- Cited by
- 95
- References
- 7
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 2 · 2023: 6 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 1 · 2016: 6 · 2015: 4 · 2014: 6 · 2013: 4 · 2012: 3
- FWCI
- 3.27
- Type
- journal article
- Language
- en
- Open access
- green
- hispana.mcu.es
- Licence
- other-oa
- Locations
- Molecular Biology of the Cell (publishedVersion)
- PubMed (publishedVersion)
- Hispana (submittedVersion, other-oa)
- Funders
- Eli Lilly and Company
- Fundación Juan March
- Instituto de Salud Carlos III
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- HDAC6, lymphocyte chemotaxis, T cell migration, transendothelial migration, cell polarity, lamellipodia, uropod, HDAC6 inhibitors, tubacin
- MeSH terms
- Histone Deacetylase 6, Acetylation, Anilides, Cell Adhesion, Cell Migration Inhibition, Cells, Cultured, Chemotaxis, Histone Deacetylases, Humans, Hydroxamic Acids, Lymphocyte Activation, T-Lymphocytes, Tubulin, Gene Expression, Cell Polarity, Gene Silencing, Protein Transport, Mutant Proteins, Histone Deacetylase Inhibitors
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