title: Nuclear transport of the serum response factor coactivator MRTF-A is downregulated at tensional homeostasis.
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.
authors.affiliation: Department of Cell Biology, UCL Institute of Ophthalmology, London, UK.
authors.forename: Karen M
authors.initials: KM
authors.lastname: McGee
authors.forename: Maria K
authors.initials: MK
authors.lastname: Vartiainen
authors.forename: Peng T
authors.initials: PT
authors.lastname: Khaw
authors.forename: Richard
authors.initials: R
authors.lastname: Treisman
authors.forename: Maryse
authors.initials: M
authors.lastname: Bailly
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D051338:Cofilin 1 / Q000096:biosynthesis / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D006706:Homeostasis; D051379:Mice; D041681:NIH 3T3 Cells; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000199:Actins; D051338:Cofilin 1; D004268:DNA-Binding Proteins; C511173:Mrtfa protein, mouse; D026362:Serum Response Factor; D015534:Trans-Activators; D014157:Transcription Factors