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| Subject Categories: Cell & Tissue Architecture | Proteins |
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| The EMBO Journal
(2002) 21, 6820–6831, doi: 10.1093/emboj/cdf682 |
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| In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylation |
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| Akihisa Matsuyama1, 2, Tadahiro Shimazu1, 3, Yuko Sumida1, 2, Akiko Saito3, Yasuhiro Yoshimatsu3, Daphné Seigneurin-Berny4, Hiroyuki Osada5, Yasuhiko Komatsu2, Norikazu Nishino2, 6, Saadi Khochbin4, Sueharu Horinouchi3 and Minoru Yoshida1, 2, 3 |
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1 Chemical Genetics Laboratory, RIKEN, Wako, Saitama 351-0198, Japan 2 CREST Research Project, Japan Science and Technology Corporation, Saitama 332-0012, Japan 3 Department of Biotechnology, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8657, Japan 4 Laboratoire de Biologie Moléculaire et Cellulaire de la Différenciation-INSERM U309, Equipe, Chromatine et Expression des Gènes, Institut Albert Bonniot, Faculté de Médecine, Domaine de la Merci, France 5 Antibiotics Laboratory, RIKEN, Wako, Saitama 351-0198, Japan 6 Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Wakamatsu, Kitakyushu 808-0196, Japan To whom correspondence should be addressed Minoru Yoshida, yoshidam@postman.riken.go.jp Received 5 April 2002; Revised 18 October 2002; Accepted 29 October 2002. |
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| Abstract |
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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,  -tubulin was identified as an HDAC6 substrate. HDAC6 deacetylated -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. |
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| Keywords: acetylation, HDAC6, microtubule, stability, tubulin |
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