title: In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylation.
abstract: Trichostatin A (TSA) inhibits all histone deacetylases (HDACs) of both class I and II, whereas trapoxin (TPX) cannot inhibit HDAC6, a cytoplasmic member of class II HDACs. We took advantage of this differential sensitivity of HDAC6 to TSA and TPX to identify its substrates. Using this approach, alpha-tubulin was identified as an HDAC6 substrate. HDAC6 deacetylated alpha-tubulin both in vivo and in vitro. Our investigations suggest that HDAC6 controls the stability of a dynamic pool of microtubules. Indeed, we found that highly acetylated microtubules observed after TSA treatment exhibited delayed drug-induced depolymerization and that HDAC6 overexpression prompted their induced depolymerization. Depolymerized tubulin was rapidly deacetylated in vivo, whereas tubulin acetylation occurred only after polymerization. We therefore suggest that acetylation and deacetylation are coupled to the microtubule turnover and that HDAC6 plays a key regulatory role in the stability of the dynamic microtubules.
authors.affiliation: Chemical Genetics Laboratory, Wako, Saitama 351-0198, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Matsuyama
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Shimazu
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sumida
authors.forename: Akiko
authors.initials: A
authors.lastname: Saito
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshimatsu
authors.forename: Daphné
authors.initials: D
authors.lastname: Seigneurin-Berny
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osada
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Komatsu
authors.forename: Norikazu
authors.initials: N
authors.lastname: Nishino
authors.forename: Saadi
authors.initials: S
authors.lastname: Khochbin
authors.forename: Sueharu
authors.initials: S
authors.lastname: Horinouchi
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000107:Acetylation; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D003703:Demecolcine / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism*; D015151:Immunoblotting; D051379:Mice; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D013997:Time Factors; D014162:Transfection; D014404:Tubulin / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010455:Peptides; D014404:Tubulin; D000431:Ethanol; C433811:HDAC6 protein, human; C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases; D003703:Demecolcine