Regulation of MKL1 via actin cytoskeleton dynamics drives adipocyte differentiation

Hiroyuki Nobusue, Nobuyuki Onishi, Takatsune Shimizu, Eiji Sugihara, Yoshinao Oki, Yuko Sumikawa, Tatsuyuki Chiyoda, Koichi Akashi, Hideyuki Saya, Koichiro Kano
2014 Nature Communications  
Cellular differentiation is regulated through activation and repression of defined transcription factors. A hallmark of differentiation is a pronounced change in cell shape, which is determined by dynamics of the actin cytoskeleton. Here we show that regulation of the transcriptional coactivator MKL1 (megakaryoblastic leukemia 1) by actin cytoskeleton dynamics drives adipocyte differentiation mediated by peroxisome proliferator-activated receptor g (PPARg), a master transcriptional regulator of
more » ... adipogenesis. Induction of adipocyte differentiation results in disruption of actin stress fibres through downregulation of RhoA-ROCK signalling. The consequent rapid increase in monomeric G-actin leads to the interaction of G-actin with MKL1, which prevents nuclear translocation of MKL1 and allows expression of PPARg followed by adipogenic differentiation. Moreover, we found that MKL1 and PPARg act in a mutually antagonistic manner in the adipocytic differentiation programme. Our findings thus provide new mechanistic insight into the relation between the dynamics of cell shape and transcriptional regulation during cellular differentiation.
doi:10.1038/ncomms4368 pmid:24569594 fatcat:w3jkujemefeb5hfscgsiqf5raq