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

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

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 γ (PPARγ), a master transcriptional regulator of 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 PPARγ followed by adipogenic differentiation. Moreover, we found that MKL1 and PPARγ 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.

Original languageEnglish
Number of pages1
JournalNature communications
Volume5
DOIs
Publication statusPublished - Jan 1 2014

Fingerprint

leukemias
Actin Cytoskeleton
Adipocytes
Peroxisome Proliferator-Activated Receptors
Actins
Leukemia
Cell Shape
Adipogenesis
Stress Fibers
Transcription Factors
Down-Regulation
regulators
Chemical activation
cells
induction
Fibers
activation
fibers

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Nobusue, H., Onishi, N., Shimizu, T., Sugihara, E., Oki, Y., Sumikawa, Y., ... Kano, K. (2014). Regulation of MKL1 via actin cytoskeleton dynamics drives adipocyte differentiation. Nature communications, 5. https://doi.org/10.1038/ncomms4368

Regulation of MKL1 via actin cytoskeleton dynamics drives adipocyte differentiation. / Nobusue, Hiroyuki; Onishi, Nobuyuki; Shimizu, Takatsune; Sugihara, Eiji; Oki, Yoshinao; Sumikawa, Yuko; Chiyoda, Tatsuyuki; Akashi, Koichi; Saya, Hideyuki; Kano, Koichiro.

In: Nature communications, Vol. 5, 01.01.2014.

Research output: Contribution to journalArticle

Nobusue, H, Onishi, N, Shimizu, T, Sugihara, E, Oki, Y, Sumikawa, Y, Chiyoda, T, Akashi, K, Saya, H & Kano, K 2014, 'Regulation of MKL1 via actin cytoskeleton dynamics drives adipocyte differentiation', Nature communications, vol. 5. https://doi.org/10.1038/ncomms4368
Nobusue, Hiroyuki ; Onishi, Nobuyuki ; Shimizu, Takatsune ; Sugihara, Eiji ; Oki, Yoshinao ; Sumikawa, Yuko ; Chiyoda, Tatsuyuki ; Akashi, Koichi ; Saya, Hideyuki ; Kano, Koichiro. / Regulation of MKL1 via actin cytoskeleton dynamics drives adipocyte differentiation. In: Nature communications. 2014 ; Vol. 5.
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