title: Regulation of adipogenesis by cytoskeleton remodelling is facilitated by acetyltransferase MEC-17-dependent acetylation of α-tubulin.
abstract: 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.
authors.affiliation: Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Wulin
authors.initials: W
authors.lastname: Yang
authors.forename: Xiangxiang
authors.initials: X
authors.lastname: Guo
authors.forename: Shermaine
authors.initials: S
authors.lastname: Thein
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sugii
authors.forename: Peter W
authors.initials: PW
authors.lastname: Baas
authors.forename: George K
authors.initials: GK
authors.lastname: Radda
authors.forename: Weiping
authors.initials: W
authors.lastname: Han
mesh_terms: D041721:3T3-L1 Cells; D000107:Acetylation; D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D003599:Cytoskeleton / Q000378:metabolism; D055785:Gene Knockdown Techniques; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism; D000074201:Katanin; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000378:metabolism; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D056565:Sirtuin 2 / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D050505:Mutant Proteins; D014404:Tubulin; D000123:Acetyltransferases; C418743:Sirt2 protein, mouse; D056565:Sirtuin 2; C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases; D000251:Adenosine Triphosphatases; D000074201:Katanin