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

研究成果: Article

16 引文 (Scopus)

摘要

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.

原文English
頁(從 - 到)4186-4200
頁數15
期刊Journal of Cell Science
127
發行號19
DOIs
出版狀態Published - 2014 一月 1

指紋

Focal Adhesions
Cell Lineage
Mesenchymal Stromal Cells
Stress Fibers
Osteogenesis
Rho Guanine Nucleotide Exchange Factors
Myosin Type II
Guanine Nucleotide Exchange Factors
Actomyosin
Proteome
Myosins
Cytoskeleton
Dexamethasone
Actins

All Science Journal Classification (ASJC) codes

  • Cell Biology

引用此文

Huang, I. H., Hsiao, C. T., Wu, J. C., Shen, R. F., Liu, C. Y., Wang, Y. K., ... 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
Huang, I. Husan ; Hsiao, Cheng Te ; Wu, Jui Chung ; Shen, Rong Fong ; Liu, Ching Yi ; Wang, Yang Kao ; Chen, Yu Chen ; Huang, Chi Ming ; del Álamo, Juan C. ; Chang, Zee Fen ; Tang, Ming Jer ; Khoo, Kay Hooi ; Kuo, Jean Cheng. / GEF-H1 controls focal adhesion signaling that regulates mesenchymal stem cell lineage commitment. 於: Journal of Cell Science. 2014 ; 卷 127, 編號 19. 頁 4186-4200.
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title = "GEF-H1 controls focal adhesion signaling that regulates mesenchymal stem cell lineage commitment",
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.",
author = "Huang, {I. Husan} and Hsiao, {Cheng Te} and Wu, {Jui Chung} and Shen, {Rong Fong} and Liu, {Ching Yi} and Wang, {Yang Kao} and Chen, {Yu Chen} and Huang, {Chi Ming} and {del {\'A}lamo}, {Juan C.} and Chang, {Zee Fen} and Tang, {Ming Jer} and Khoo, {Kay Hooi} and Kuo, {Jean Cheng}",
year = "2014",
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Huang, IH, Hsiao, CT, Wu, JC, Shen, RF, Liu, CY, Wang, YK, Chen, YC, Huang, CM, del Álamo, JC, Chang, ZF, Tang, MJ, Khoo, KH & Kuo, JC 2014, 'GEF-H1 controls focal adhesion signaling that regulates mesenchymal stem cell lineage commitment', Journal of Cell Science, 卷 127, 編號 19, 頁 4186-4200. https://doi.org/10.1242/jcs.150227

GEF-H1 controls focal adhesion signaling that regulates mesenchymal stem cell lineage commitment. / Huang, I. Husan; Hsiao, Cheng Te; Wu, Jui Chung; Shen, Rong Fong; Liu, Ching Yi; Wang, Yang Kao; Chen, Yu Chen; Huang, Chi Ming; del Álamo, Juan C.; Chang, Zee Fen; Tang, Ming Jer; Khoo, Kay Hooi; Kuo, Jean Cheng.

於: Journal of Cell Science, 卷 127, 編號 19, 01.01.2014, p. 4186-4200.

研究成果: Article

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T1 - GEF-H1 controls focal adhesion signaling that regulates mesenchymal stem cell lineage commitment

AU - Huang, I. Husan

AU - Hsiao, Cheng Te

AU - Wu, Jui Chung

AU - Shen, Rong Fong

AU - Liu, Ching Yi

AU - Wang, Yang Kao

AU - Chen, Yu Chen

AU - Huang, Chi Ming

AU - del Álamo, Juan C.

AU - Chang, Zee Fen

AU - Tang, Ming Jer

AU - Khoo, Kay Hooi

AU - Kuo, Jean Cheng

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

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