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EMBO Rep. 2011 Sep 1;12(9):963-70. doi: 10.1038/embor.2011.141.

Nuclear transport of the serum response factor coactivator MRTF-A is downregulated at tensional homeostasis.

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  • 1Department of Cell Biology, UCL Institute of Ophthalmology, London, UK.

Abstract

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.

PMID:
21799516
[PubMed - indexed for MEDLINE]
PMCID:
PMC3166461
Free PMC Article
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