The insulin-PI3K-Rac1 axis contributes to terminal adipocyte differentiation through regulation of actin cytoskeleton dynamics

Haruko Kunitomi, Yoshinao Oki, Nobuyuki Onishi, Koichiro Kano, Kouji Banno, Daisuke Aoki, Hideyuki Saya, Hiroyuki Nobusue

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Adipocyte differentiation is accompanied by a pronounced change in the actin cytoskeleton characterized by the reorganization of filamentous (F)-actin stress fibers into cortical F-actin structures. We previously showed that depolymerization of F-actin stress fibers induced by inactivation of RhoA–ROCK (Rho-associated kinase) signaling acts as a trigger for adipocyte differentiation. The relevance and underlying mechanism of the formation of cortical F-actin structures from depolymerized actin during adipocyte differentiation have remained unclear, however. We have now examined the mechanistic relation between actin dynamics and adipogenic induction. Transient exposure to the actin-depolymerizing agent latrunculin A (LatA) supported the formation of adipocyte-associated cortical actin structures and the completion of terminal adipocyte differentiation in the presence of insulin, whereas long-term exposure to LatA prevented such actin reorganization as well as terminal adipogenesis. Moreover, these effects of insulin were prevented by inhibition of phosphatidylinositol 3-kinase (PI3K)–Rac1 signaling and the actin-related protein 2/3 (Arp2/3) complex which is a critical component of the cortical actin networks. Our findings thus suggest that the insulin-PI3K-Rac1 axis leads to the formation of adipocyte-associated cortical actin structures which is essential for the completion of adipocyte differentiation.

Original languageEnglish
Pages (from-to)165-174
Number of pages10
JournalGenes to Cells
Volume25
Issue number3
DOIs
Publication statusPublished - 2020 Mar 1

Keywords

  • Rac1
  • actin cytoskeleton
  • adipocyte differentiation
  • insulin
  • phosphatidylinositol 3-kinase (PI3K)

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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