HDAC6 is a microtubule-associated deacetylase.
Reversible acetylation of alpha-tubulin has been implicated in regulating microtubule stability and function. The distribution of acetylated alpha-tubulin is tightly controlled and stereotypic. Acetylated alpha-tubulin is most abundant in stable microtubules but is absent from dynamic cellular structures such as neuronal growth cones and the leading edges of fibroblasts. However, the enzymes responsible for regulating tubulin acetylation and deacetylation are not known. Here we report that a member of the histone deacetylase family, HDAC6, functions as a tubulin deacetylase. HDAC6 is localized exclusively in the cytoplasm, where it associates with microtubules and localizes with the microtubule motor complex containing p150(glued) (ref. 3). In vivo, the overexpression of HDAC6 leads to a global deacetylation of alpha-tubulin, whereas a decrease in HDAC6 increases alpha-tubulin acetylation. In vitro, purified HDAC6 potently deacetylates alpha-tubulin in assembled microtubules. Furthermore, overexpression of HDAC6 promotes chemotactic cell movement, supporting the idea that HDAC6-mediated deacetylation regulates microtubule-dependent cell motility. Our results show that HDAC6 is the tubulin deacetylase, and provide evidence that reversible acetylation regulates important biological processes beyond histone metabolism and gene transcription.
Hubbert
Charlotte
C
Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina 27710, USA.
Guardiola
Amaris
A
Shao
Rong
R
Kawaguchi
Yoshiharu
Y
Ito
Akihiro
A
Nixon
Andrew
A
Yoshida
Minoru
M
Wang
Xiao-Fan
XF
Yao
Tso-Pang
TP
D016475:3T3 Cells; D000107:Acetylation; D000818:Animals; D002633:Chemotaxis; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*
D008869:Microtubule-Associated Proteins; D014404:Tubulin; C433811:HDAC6 protein, human; C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases