RhoGDIβ Inhibits Bone Morphogenetic Protein 4 (BMP4)-induced Adipocyte Lineage Commitment and Favors Smooth Muscle-like Cell Differentiation

J Biol Chem. 2015 Apr 24;290(17):11119-29. doi: 10.1074/jbc.M114.608075. Epub 2015 Mar 16.


The integration of signals involved in deciding the fate of mesenchymal stem cells is largely unknown. We used proteomics profiling to identify RhoGDIβ, an inhibitor of the small G-protein Rho family, as a component that regulates commitment of C3H10T1/2 mesenchymal stem cells to the adipocyte or smooth muscle cell lineage in response to bone morphogenetic protein 4 (BMP4). RhoGDIβ is notably down-regulated during BMP4-induced adipocytic lineage commitment of C3H10T1/2 mesenchymal stem cells, and this involves the cytoskeleton-associated protein lysyl oxidase. Excess RhoGDIβ completely prevents BMP4-induced commitment to the adipocyte lineage and simultaneously stimulates smooth muscle cell commitment by suppressing the activation of Rac1. Overexpression of RhoGDIβ induces stress fibers of F-actin by a process involving phosphomyosin light chain, indicating that cytoskeletal tension regulated by RhoGDIβ contributes to determining adipocyte versus myocyte commitment. Furthermore, the overexpression of RacV12 (constitutively active form of Rac1) totally rescues the inhibition of adipocyte commitment by RhoGDIβ, simultaneously preventing formation of the smooth muscle-like phenotype and disrupting the stress fibers in cells overexpressing RhoGDIβ. Collectively, these results indicate that RhoGDIβ functions as a novel BMP4 signaling target that regulates adipogenesis and myogensis.

Keywords: Adipocyte; BMP4; Cytoskeleton; Lysyl Oxidase; Mesenchymal Stem Cells (MSCs); Ras-related C3 Botulinum Toxin Substrate 1 (Rac1); RhoGDIβ; Smooth Muscle-like Cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism*
  • Animals
  • Bone Morphogenetic Protein 4 / genetics
  • Bone Morphogenetic Protein 4 / metabolism*
  • Cell Differentiation / physiology*
  • Cell Line
  • Mice
  • Muscle Development / physiology*
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / metabolism*
  • Neuropeptides / genetics
  • Neuropeptides / metabolism
  • Signal Transduction / physiology*
  • Stress Fibers / genetics
  • Stress Fibers / metabolism
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism
  • rho Guanine Nucleotide Dissociation Inhibitor beta / genetics
  • rho Guanine Nucleotide Dissociation Inhibitor beta / metabolism*


  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Neuropeptides
  • Rac1 protein, mouse
  • rho Guanine Nucleotide Dissociation Inhibitor beta
  • rac1 GTP-Binding Protein