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Muscle-Specific Signaling Mechanism That Links Actin Dynamics to Serum Response Factor

机译：将肌动蛋白动力学与血清反应因子联系起来的特定于肌肉的信号传导机制

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Myocardin and the myocardin-related transcription factors (MRTFs) MRTF-A and MRTF-B are coactivators for serum response factor (SRF), which regulates genes involved in cell proliferation, migration, cytoskeletal dynamics, and myogenesis. MRTF-A has been shown to translocate to the nucleus and activate SRF in response to Rho signaling and actin polymerization. Previously, we described a muscle-specific actin-binding protein named striated muscle activator of Rho signaling (STARS) that also activates SRF through a Rho-dependent mechanism. Here we show that STARS activates SRF by inducing the nuclear translocation of MRTFs. The STARS-dependent nuclear import of MRTFs requires RhoA and actin polymerization, and the actin-binding domain of STARS is necessary and sufficient for this activity. A knockdown of endogenous STARS expression by using small interfering RNA significantly reduced SRF activity in differentiated C2C12 skeletal muscle cells and cardiac myocytes. The ability of STARS to promote the nuclear localization of MRTFs and SRF-mediated transcription provides a potential muscle-specific mechanism for linking changes in actin dynamics and sarcomere structure with striated muscle gene expression.
机译：心肌素和心肌相关转录因子（MRTF）MRTF-A和MRTF-B是血清反应因子（SRF）的共激活因子，后者调节涉及细胞增殖，迁移，细胞骨架动力学和肌生成的基因。已经显示，MRTF-A响应Rho信号转导和肌动蛋白聚合而易位至细胞核并激活SRF。以前，我们描述了一种名为Rho信号的条纹肌激活物（STARS）的肌肉特异性肌动蛋白结合蛋白，该蛋白也通过Rho依赖性机制激活SRF。在这里，我们表明STARS通过诱导MRTF的核易位激活SRF。 MRTF的STARS依赖核输入需要RhoA和肌动蛋白聚合，而STARS的肌动蛋白结合域对于这种活性是必要和充分的。通过使用小的干扰RNA敲低内源性STARS表达，可显着降低分化的C2C12骨骼肌细胞和心肌细胞中的SRF活性。 STARS促进MRTF的核定位和SRF介导的转录的能力为肌动蛋白动力学和肌节结构变化与横纹肌基因表达之间的联系提供了潜在的肌肉特异性机制。

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