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The cytoskeleton-associated PDZ-LIM protein, ALP, acts on serum response factor activity to regulate muscle differentiation

机译:细胞骨架相关的PDZ-LIM蛋白ALP作用于血清反应因子活性以调节肌肉分化

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In this report, an antisense RNA strategy has allowed us to show that disruption of ALP expression affects the expression of the muscle transcription factors myogenin and MyoD, resulting in the inhibition of muscle differentiation. Introduction of a MyoD expression construct into ALP-antisense cells is sufficient to restore the capacity of the cells to differentiate, illustrating that ALP function occurs upstream of MyoD. It is known that MyoD is under the control of serum response factor (SRF), a transcriptional regulator whose activity is modulated by actin dynamics. A dramatic reduction of actin filament bundles is observed in ALP-antisense cells and treatment of these cells with the actin-stabilizing drug jasplakinolide stimulates SRF activity and restores the capacity of the cells to differentiate. Furthermore, we show that modulation of ALP expression influences SRF activity, the level of its coactivator, MAL, and muscle differentiation. Collectively, these results suggest a critical role of ALP on muscle differentiation, likely via cytoskeletal. regulation of SRF.
机译:在此报告中,反义RNA策略使我们能够证明ALP表达的破坏会影响肌肉转录因子myogenin和MyoD的表达,从而抑制肌肉分化。将MyoD表达构建体引入ALP反义细胞足以恢复细胞的分化能力,这说明ALP功能发生在MyoD的上游。已知MyoD受血清反应因子(SRF)的控制,SRF是一种转录调节剂,其活性受肌动蛋白动力学调节。在ALP反义细胞中观察到肌动蛋白丝束的急剧减少,用肌动蛋白稳定药物jasplakinolide处理这些细胞可刺激SRF活性并恢复细胞分化的能力。此外,我们显示出对ALP表达的调节会影响SRF活性,其辅助激活剂,MAL和肌肉分化的水平。总体而言,这些结果表明ALP可能通过细胞骨架在肌肉分化中发挥关键作用。 SRF的规定。

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