Nuclear transport of the serum response factor coactivator MRTF‐A is downregulated at tensional homeostasis
Nuclear transport of the serum response factor coactivator MRTF‐A is downregulated at tensional homeostasis
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.
- London Research Institute United Kingdom
- UCL Institute of Ophthalmology United Kingdom
- Moorfields Eye Hospital NHS Foundation Trust United Kingdom
- Moorfields Eye Hospital United Kingdom
- Cancer Research UK United Kingdom
Cofilin 1, Serum Response Factor, Active Transport, Cell Nucleus, Down-Regulation, Actins, Cell Line, DNA-Binding Proteins, Mice, Stress, Physiological, NIH 3T3 Cells, Trans-Activators, Animals, Homeostasis, Signal Transduction, Transcription Factors
Cofilin 1, Serum Response Factor, Active Transport, Cell Nucleus, Down-Regulation, Actins, Cell Line, DNA-Binding Proteins, Mice, Stress, Physiological, NIH 3T3 Cells, Trans-Activators, Animals, Homeostasis, Signal Transduction, Transcription Factors
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