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.
Regulation of adipogenesis by cytoskeleton remodelling is facilitated by acetyltransferase MEC-17-dependent acetylation of α-tubulin
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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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