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Título : Lymphocyte chemotaxis is regulated by histone deacetylase 6, independently of its deacetylase activity
Autor : Cabrero, J. Román; Serrador, Juan M.; Barreiro, Olga; Mittelbrunn, María; Naranjo-Suárez, Salvador; Martín-Cófreces, Noa; Vicente-Manzanares, Miguel; Mazitschek, Ralph; Bradner, James E.; Ávila, Jesús; Valenzuela-Fernández, Agustín; Sánchez-Madrid, Francisco
Palabras clave : Histone deacetylase 6
Fecha de publicación : 31-may-2006
Editor: American Society for Cell Biology
Citación : Molecular Biology of the Cell (2006) Vol. 17, Issue 8, 3435-3445
Resumen: 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.
Descripción : Supplementary material at http://www.molbiolcell.org/cgi/content/full/E06-01-0008/DC1
Versión del editor: http://www.molbiolcell.org/cgi/content/abstract/E06-01-0008v1
URI : http://hdl.handle.net/10261/8148
ISSN: 1059-1524 (print)
1939-4586 (online)
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