GEF-H1 controls focal adhesion signaling that regulates mesenchymal stem cell lineage commitment.
GEF-H1 controls focal adhesion signaling that regulates mesenchymal stem cell lineage commitment.
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DOI：
10.1242/jcs.150227
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发表时间：
2014-10-01
影响因子：
4
通讯作者：
Kuo JC
中科院分区：
文献类型：
--
作者：
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
局灶性粘连（FAs）经过成熟，最终在大小和组成上发生变化，从而调节粘连、细胞骨架重塑和分化。虽然众所周知，间充质干细胞（MSCs）的成骨刺激驱动FA成熟、肌动蛋白组织和应激纤维极化，但FA蛋白组成调节的FA介导信号在多大程度上决定MSC承诺仍是未知的。在这里，我们证明，在地塞米松（成骨诱导）治疗后，鸟嘌呤核苷酸交换因子H1 （GEF-H1，也称为Rho鸟嘌呤核苷酸交换因子2，由ARHGEF2编码）在FAs中显著富集。GEF-H1的扰动以不依赖于肌动球蛋白收缩性的方式抑制FA形成、各向异性应力纤维取向和MSC成骨。为了确定GEF-H1在MSC成骨中的作用，我们探索了GEF-H1调节的FA蛋白质组，发现非肌肉肌球蛋白- ii重链b （NMIIB，也称为肌球蛋白-10，由MYH10编码）是FAs中GEF-H1的靶标。抑制NMIIB靶向FAs可抑制间充质干细胞中FA的形成、应力纤维极化、细胞刚度和成骨承诺。我们的数据证明了FA信号在指定MSC承诺中的作用。
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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影响因子：
3.4
作者：
Grosheva, Inna;Vittitow, Jason L.;Bershadsky, Alexander D.
通讯作者：
Bershadsky, Alexander D.
DOI：
10.1073/pnas.0408239102
发表时间：
2005-03-29
影响因子：
11.1
作者：
Kondo, T;Johnson, SA;Hashino, E
通讯作者：
Hashino, E
DOI：
10.1073/pnas.0903269107
发表时间：
2010-03-16
影响因子：
11.1
作者：
Kilian, Kristopher A.;Bugarija, Branimir;Mrksich, Milan
通讯作者：
Mrksich, Milan
影响因子：
6.4
作者：
Hung, SC;Yang, DM;Yang, WK
通讯作者：
Yang, WK
影响因子：
--
作者：
Costa KD
通讯作者：
Costa KD