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Originally published as MBC in Press, 10.1091/mbc.E06-01-0008 on May 31, 2006

Vol. 17, Issue 8, 3435-3445, August 2006

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Lymphocyte Chemotaxis Is Regulated by Histone Deacetylase 6, Independently of Its Deacetylase ActivityFormula

J. Román Cabrero*,{dagger}, Juan M. Serrador*,{dagger},{ddagger}, Olga Barreiro*, María Mittelbrunn*, Salvador Naranjo-Suárez*, Noa Martín-Cófreces*, Miguel Vicente-Manzanares*, Ralph Mazitschek§, James E. Bradner§, Jesús Ávila||, Agustín Valenzuela-Fernández*, and Francisco Sánchez-Madrid*

*Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain; {ddagger}Centro Nacional de Investigaciones Cardiovasculares (CNIC), Unidad Mixta CNIC-Universitat de Valencia, 46010 Valencia, Spain; §Chemical Biology Program, The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02141; and ||Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain

Submitted January 4, 2006; Revised May 17, 2006; Accepted May 18, 2006
Monitoring Editor: Martin A. Schwartz

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.


This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-01-0008) on May 31, 2006.

Formula The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

{dagger} These authors contributed equally to this work.

Address correspondence to: F. Sánchez-Madrid ( fsanchez.hlpr{at}salud.madrid.org)

Abbreviations used: TSA, trichostatin A; NCD, nocodazole; TXL, Taxol; PBL, peripheral blood lymphocyte; FN, fibronectin; MTOC, microtubule-organizing center; Tbc, tubacin; HUVEC, human umbilical vein endothelial cells




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