Cabrero J Román, Serrador Juan M, Barreiro Olga, Mittelbrunn María, Naranjo-Suárez Salvador, Martín-Cófreces Noa, Vicente-Manzanares Miguel, Mazitschek Ralph, Bradner James E, Avila Jesús, Valenzuela-Fernández Agustín, Sánchez-Madrid Francisco
Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain.
Mol Biol Cell. 2006 Aug;17(8):3435-45. doi: 10.1091/mbc.e06-01-0008. Epub 2006 May 31.
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.
在本研究中，我们探讨了具有微管蛋白去乙酰化酶活性的II型组蛋白去乙酰化酶HDAC6在淋巴细胞极性、运动性和迁移中的作用。HDAC6定位于动态亚细胞结构，如迁移T细胞中的前缘板状伪足和尾足。然而，HDAC6的活性似乎与迁移淋巴细胞的极性无关。在新鲜分离的淋巴细胞和T细胞系中过表达HDAC6可增加趋化因子介导的淋巴细胞迁移及其在剪切流下的跨内皮迁移。相应地，T细胞中HDAC6表达的敲低降低了它们的趋化能力。使用HDAC6抑制剂（曲古抑菌素、tubacin）、其他结构相关分子（niltubacin、MAZ-1391）和HDAC6失活突变体进行的额外实验表明，HDAC6的去乙酰化酶活性不参与该分子对细胞迁移的调节作用。我们的结果表明，HDAC6在T淋巴细胞的趋化作用中起重要作用，这与其微管蛋白去乙酰化酶活性无关。
