Regulatory roles of fibronectin and integrin α5 in reorganization of the actin cytoskeleton and completion of adipogenesis

Megumi Uetaki, Nobuyuki Onishi, Yoshinao Oki, Takatsune Shimizu, Eiji Sugihara, Oltea Sampetrean, Takashi Watanabe, Hisano Yanagi, Kiyoshi Suda, Hiroya Fujii, Koichiro Kano, Hideyuki Saya, Hiroyuki Nobusue

Research output: Contribution to journalArticlepeer-review

Abstract

Cellular differentiation is characterized by changes in cell morphology that are largely determined by actin dynamics. We previously showed that depolymerization of the actin cytoskeleton triggers the differentiation of preadipocytes into mature adipocytes as a result of inhibition of the transcriptional coactivator activity of megakaryoblastic leukemia 1 (MKL1). The extracellular matrix (ECM) influences cell morphology via interaction with integrins, and reorganization of the ECM is associated with cell differentiation. Here we show that interaction between actin dynamics and ECM rearrangement plays a key role in adipocyte differentiation. We found that depolymerization of the actin cytoskeleton precedes disruption and degradation of fibrillar fibronectin (FN) structures at the cell surface after the induction of adipogenesis in cultured preadipocytes. A FN matrix suppressed both reorganization of the actin cytoskeleton into the pattern characteristic of adipocytes and terminal adipocyte differentiation, and these inhibitory effects were overcome by knockdown of integrin α5 (ITGα5). Peroxisome proliferator-activated receptor γ was required for down-regulation of FN during adipocyte differentiation, and MKL1 was necessary for the expression of ITGα5. Our findings suggest that cell-autonomous down-regulation of FN-ITGα5 interaction contributes to reorganization of the actin cytoskeleton and completion of adipocyte differentiation.

Original languageEnglish
Pages (from-to)ar78
JournalMolecular biology of the cell
Volume33
Issue number9
DOIs
Publication statusPublished - 2022 Aug 1

ASJC Scopus subject areas

  • Medicine(all)

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