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bioRxiv · 10.1101/395962

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

Montel, L.·Sotiropoulos, A.·Henon, S.
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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 (hours) accumulation, with a global increase in polymerized actin. Conversely, high strain induced actin depolymerization at intermediate times, associated with cytoplasmic MRTF accumulation.

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Montel, L., Sotiropoulos, A., Henon, S.. 2018-08-20. The nature and intensity of mechanical stimulation drive different dynamics of MRTF-A nuclear redistribution after actin remodeling in myoblasts. https://doi.org/10.1101/395962

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