期刊
EMBO REPORTS
卷 12, 期 9, 页码 963-970出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/embor.2011.141
关键词
actin dynamics; cofilin; MRTF-A/MAL-SRF pathway; tissue tension
资金
- Medical Research Council [GO500927]
- Royal Society
- Cancer Research UK
- National Institute for Health Research Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital
- University College London Institute of Ophthalmology
- Wellcome Trust
- Medical Research Council
- Medical Research Council [G0500927] Funding Source: researchfish
- MRC [G0500927] Funding Source: UKRI
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.
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