GEF-H1 controls focal adhesion signaling that regulates mesenchymal stem cell lineage commitment

I. Husan Huang, Cheng Te Hsiao, Jui Chung Wu, Rong Fong Shen, Ching Yi Liu, Yang Kao Wang, Yu Chen Chen, Chi Ming Huang, Juan C. del Álamo, Zee Fen Chang, Ming Jer Tang, Kay Hooi Khoo, Jean Cheng Kuo

    Research output: Contribution to journalArticle

    19 Citations (Scopus)

    Abstract

    Focal adhesions (FAs) undergo maturation that culminates in size and composition changes that modulate adhesion, cytoskeleton remodeling and differentiation. Although it is well recognized that stimuli for osteogenesis of mesenchymal stem cells (MSCs) drive FA maturation, actin organization and stress fiber polarization, the extent to which FA-mediated signals regulated by the FA protein composition specifies MSC commitment remains largely unknown. Here, we demonstrate that, upon dexamethasone (osteogenic induction) treatment, guanine nucleotide exchange factor H1 (GEF-H1, also known as Rho guanine nucleotide exchange factor 2, encoded by ARHGEF2) is significantly enriched in FAs. Perturbation of GEF-H1 inhibits FA formation, anisotropic stress fiber orientation and MSC osteogenesis in an actomyosin-contractility-independent manner. To determine the role of GEF-H1 in MSC osteogenesis, we explore the GEF-H1-modulated FA proteome that reveals non-muscle myosin-II heavy chain-B (NMIIB, also known as myosin-10, encoded by MYH10) as a target of GEF-H1 in FAs. Inhibition of targeting NMIIB into FAs suppresses FA formation, stress fiber polarization, cell stiffness and osteogenic commitments in MSCs. Our data demonstrate a role for FA signaling in specifying MSC commitment.

    Original languageEnglish
    Pages (from-to)4186-4200
    Number of pages15
    JournalJournal of Cell Science
    Volume127
    Issue number19
    DOIs
    Publication statusPublished - 2014

    Keywords

    • Focal adhesions
    • Mesenchymal stem cell
    • Osteogenesis
    • Stress fiber

    ASJC Scopus subject areas

    • Cell Biology

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  • Cite this

    Huang, I. H., Hsiao, C. T., Wu, J. C., Shen, R. F., Liu, C. Y., Wang, Y. K., Chen, Y. C., Huang, C. M., del Álamo, J. C., Chang, Z. F., Tang, M. J., Khoo, K. H., & Kuo, J. C. (2014). GEF-H1 controls focal adhesion signaling that regulates mesenchymal stem cell lineage commitment. Journal of Cell Science, 127(19), 4186-4200. https://doi.org/10.1242/jcs.150227