Department of Cell Biology, UCL Institute of Ophthalmology, London, UK.
EMBO Rep. 2011 Sep 1;12(9):963-70. doi: 10.1038/embor.2011.141.
The serum response factor (SRF) coactivator myocardin-related transcription factor A (MAL/MKL1/MRTF-A), the nuclear transport and activity of which is regulated by monomeric actin, has been implicated in tension-based regulation of SRF-mediated transcriptional activity. However, the mechanisms involved remain unclear. We used fibroblasts grown within collagen matrices to explore whether MRTF-A transport is regulated by tissue tension. We show that MRTF-A nuclear accumulation following stimulation with serum, actin drugs or acute mechanical stress is prevented within mechanically loaded, anchored matrices at tensional homeostasis. This is accompanied by a higher G/F actin ratio, defective nuclear import and increased cofilin expression. We propose that tension regulates MRTF-A/SRF activity through cofilin-mediated modulation of actin dynamics.
血清反应因子（SRF）共激活因子心肌营养素相关转录因子 A（MAL/MKL1/MRTF-A）的核转运和活性受单体肌动蛋白调节，它参与了基于张力的 SRF 介导的转录活性的调节。然而，涉及的机制仍不清楚。我们使用在胶原基质中生长的成纤维细胞来探索 MRTF-A 的运输是否受到组织张力的调节。我们发现，在用血清、肌动蛋白药物或急性机械应激刺激后，在机械加载的、固定的基质中，张力平衡时，MRTF-A 的核积累被阻止。这伴随着更高的 G/F 肌动蛋白比、核输入缺陷和 cofilin 表达增加。我们提出，张力通过肌动蛋白动力学的 cofilin 介导调节来调节 MRTF-A/SRF 活性。
