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

• DOI: 10.1242/jcs.150227
• Publication Date: 2014-08-09T04:42:48Z
• Authors: 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
• Keywords: 0301 basic medicine; Focal Adhesions; 03 medical and health sciences; Osteogenesis; 13. Climate action; Humans; Cell Differentiation; Cell Lineage; Mesenchymal Stem Cells; 10. No inequality; Rho Guanine Nucleotide Exchange Factors; Research Article; Signal Transduction

Focal adhesions (FAs) undergo maturation culminating in size and composition changes that modulate adhesion, cytoskeleton remodeling and differentiation. While 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) 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) 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 FA signaling in specifying MSC commitment.