Cytoskeleton remodelling is a prerequisite step for the morphological transition from preadipocytes to mature adipocytes. Although microtubules play a pivotal role in organizing cellular structure, regulation of microtubule dynamics during adipogenesis remains unclear. In the present paper we show that acetylation of α-tubulin is up-regulated during adipogenesis, and adipocyte development is dependent on α-tubulin acetylation, as expression of an acetylation-resistant α-tubulin mutant significantly inhibits adipogenesis. Moreover, acetylation of α-tubulin is under the control of the acetyltransferase MEC-17 and deacetylases SIRT2 (Sirtuin 2) and HDAC6 (histone deacetylase 6). Adipocyte development is inhibited in MEC-17-knockdown cells, but enhanced in MEC-17-overexpressing cells. Finally, we show that katanin, a microtubule-severing protein with enhanced activity on acetylated α-tubulin, is actively involved in adipogenesis. We propose that co-ordinated up-regulation of α-tubulin acetylation initiates cytoskeleton remodelling by promoting α-tubulin severing by katanin which, in turn, allows expansion of lipid droplets and accelerates the morphological transition toward mature adipocytes.
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Research Article|
January 09 2013
Regulation of adipogenesis by cytoskeleton remodelling is facilitated by acetyltransferase MEC-17-dependent acetylation of α-tubulin
Wulin Yang;
Wulin Yang
*Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), Singapore
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Xiangxiang Guo;
Xiangxiang Guo
*Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), Singapore
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Shermaine Thein;
Shermaine Thein
*Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), Singapore
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Feng Xu;
Feng Xu
†Singapore Institute for Clinical Sciences, A*STAR, Singapore
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Shigeki Sugii;
Shigeki Sugii
*Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), Singapore
‡Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore
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Peter W. Baas;
Peter W. Baas
§Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, U.S.A.
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George K. Radda;
George K. Radda
*Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), Singapore
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Weiping Han
Weiping Han
1
*Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), Singapore
‡Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore
∥Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
¶Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
July 16 2012
Revision Received:
November 02 2012
Accepted:
November 05 2012
Accepted Manuscript online:
November 05 2012
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 449 (3): 605–612.
Article history
Received:
July 16 2012
Revision Received:
November 02 2012
Accepted:
November 05 2012
Accepted Manuscript online:
November 05 2012
Citation
Wulin Yang, Xiangxiang Guo, Shermaine Thein, Feng Xu, Shigeki Sugii, Peter W. Baas, George K. Radda, Weiping Han; Regulation of adipogenesis by cytoskeleton remodelling is facilitated by acetyltransferase MEC-17-dependent acetylation of α-tubulin. Biochem J 1 February 2013; 449 (3): 605–612. doi: https://doi.org/10.1042/BJ20121121
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