β1 integrin and organized actin filaments facilitate cardiomyocytes-specific RhoA-dependent activation of the skeletal α-actin promoter

Lei Wei, Lu Wang, James A. Carson, James E. Agan, Kyoko Imanaka-Yoshida, Robert J. Schwartz

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Activation of RhoA GTPase causes actin filament bundling into stress fibers, integrin clustering, and focal adhesion formation through its action on actin cytoskeleton organization. RhoA also regulates transcriptional activity of serum response factor (SRF). Recent studies in NIH 3T3 fibroblasts have shown that SRF activation by RhoA does not require an organized cytoskeleton and may be regulated by G-actin level. In cardiac myocytes, the organization of actin fibers into myofibrils is one of the primary characteristics of cardiac differentiation and hypertrophy. The primary purpose of this study was to examine if RhoA regulates SRF-dependent gene expression in neonatal cardiomyocytes in a manner different from that observed in fibroblasts. Our results show that RhoA-dependent skeletal α-actin promoter activation requires β1 integrin and a functional cytoskeleton in cardiomyocytes but not in NIH 3T3 fibroblasts. Activation of the α-actin promoter by RhoA is greatly potentiated (up to 15-fold) by co-expression of the integrin β1A or β1D isoform but is significantly reduced by 70% with a co-expressed dominant negative mutant of β1 integrin. Furthermore, clustering of β1 integrin with anti-β1 integrin antibodies potentiates synergistic RhoA and β1 integrin activation of the α-actin promoter. Cytochalasin D and latrunculin B, inhibitors of actin polymerization, significantly reduced RhoA-induced activation of the α-actin promoter. Jasplakinolide, an actin polymerizing agent, mimics the synergistic effect of RhoA and β1 integrin on the actin promoter. These observations support the concept that RhoA regulates SRF-dependent cardiac gene expression through cross-talk with β1 integrin signal pathway via an organized actin cytoskeleton.

Original languageEnglish (US)
Pages (from-to)785-796
Number of pages12
JournalFASEB Journal
Volume15
Issue number3
DOIs
StatePublished - 2001

Keywords

  • Actin polymerization
  • Cardiac hypertrophy
  • Serum response factor

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'β1 integrin and organized actin filaments facilitate cardiomyocytes-specific RhoA-dependent activation of the skeletal α-actin promoter'. Together they form a unique fingerprint.

  • Cite this