RhoGDIβ inhibits bone morphogenetic protein 4 (BMP4)-induced adipocyte lineage commitment and favors smooth muscle-like cell differentiation

Hai Yan Huang, Wen Ting Zhang, Wen Yan Jiang, Su Zhen Chen, Yang Liu, Xin Ge, Xi Li, Yong Jun Dang, Bo Wen, Xiao Hui Liu, Hao Jie Lu, Qi Qun Tang

Research output: Contribution to journalArticlepeer-review

Abstract

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 stimulatessmoothmuscle cellcommitmentby 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 RhoGDIβcontributes 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.

Original languageEnglish (US)
Pages (from-to)11119-11129
Number of pages11
JournalJournal of Biological Chemistry
Volume290
Issue number17
DOIs
StatePublished - Apr 24 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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