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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Active Transport, Cell Nucleus
  • Animals
  • Cell Line
  • Cofilin 1 / biosynthesis
  • Cofilin 1 / metabolism
  • DNA-Binding Proteins / metabolism
  • Down-Regulation
  • Homeostasis*
  • Mice
  • NIH 3T3 Cells
  • Serum Response Factor / genetics
  • Serum Response Factor / metabolism*
  • Signal Transduction
  • Stress, Physiological
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism

Substances

  • Actins
  • Cofilin 1
  • DNA-Binding Proteins
  • Mrtfa protein, mouse
  • Serum Response Factor
  • Trans-Activators
  • Transcription Factors