The nature and intensity of mechanical stimulation drive different dynamics of MRTF-A nuclear redistribution after actin remodeling in myoblasts

Abstract : Serum response factor and its cofactor myocardin-related transcription factor (MRTF) are key elements of muscle-mass adaptation to workload. The transcription of target genes is activated when MRTF is present in the nucleus. The localization of MRTF is controlled by its binding to G-actin. Thus, the pathway can be mechanically activated through the mechanosensitivity of the actin cytoskeleton. The pathway has been widely investigated from a biochemical point of view, but its mechanical activation and the timescales involved are poorly understood. Here, we applied local and global mechanical cues to myoblasts through two custom-built set-ups, magnetic tweezers and stretchable substrates. Both induced nuclear accumulation of MRTF-A. However, the dynamics of the response varied with the nature and level of mechanical stimulation and correlated with the polymerization of different actin sub-structures. Local repeated force induced local actin polymerization and nuclear accumulation of MRTF-A by 30 minutes, whereas a global static strain induced both rapid (minutes) transient nuclear accumulation, associated with the polymerization of an actin cap above the nucleus, and long-term accumulation, with a global increase in polymerized actin. Conversely, high strain induced actin depolymerization at intermediate times, associated with cytoplasmic MRTF accumulation.
Complete list of metadatas

Cited literature [49 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02196885
Contributor : Myriam Bodescot <>
Submitted on : Monday, July 29, 2019 - 4:09:26 PM
Last modification on : Friday, October 25, 2019 - 11:02:17 AM

File

journal.pone.0214385.pdf
Publication funded by an institution

Identifiers

Collections

Citation

Lorraine Montel, Athanassia Sotiropoulos, Sylvie Hénon. The nature and intensity of mechanical stimulation drive different dynamics of MRTF-A nuclear redistribution after actin remodeling in myoblasts. PLoS ONE, Public Library of Science, 2019, 14 (3), pp.e0214385. ⟨10.1371/journal.pone.0214385⟩. ⟨inserm-02196885⟩

Share

Metrics

Record views

55

Files downloads

53