The cytoskeleton-associated PDZ-LIM protein, ALP, acts on serum response factor activity to regulate muscle differentiation
The cytoskeleton-associated PDZ-LIM protein, ALP, acts on serum response factor activity to regulate muscle differentiation
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DOI：
10.1091/mbc.e06-09-0815
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发表时间：
2007-05-01
影响因子：
3.3
通讯作者：
Beckerle, Mary C.
中科院分区：
文献类型：
--
作者：
Pomies, Pascal;Pashmforoush, Mohammad;Beckerle, Mary C.
在这份报告中，反义RNA策略使我们能够表明，ALP表达的中断影响肌肉转录因子肌细胞生成素和MyoD的表达，导致肌肉分化的抑制。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，这表明ALP功能发生在MyoD的上游。已知MyoD受血清反应因子（SRF）控制，血清反应因子是一种转录调节因子，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，并且用肌动蛋白稳定药物jasplakinaline处理这些细胞刺激SRF活性并恢复细胞分化的能力。此外，我们表明，调节ALP表达影响SRF活性，其辅激活因子，MAL的水平，和肌肉分化。总的来说，这些结果表明ALP对肌肉分化的关键作用，可能通过细胞骨架。SRF规范。
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.