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Communication

Interrelation between α-Cardiac Actin Treadmilling and Myocardin-Related Transcription Factor-A Nuclear Shuttling in Cardiomyocytes

1
Institut de Biologie Paris-Seine (IBPS), CNRS UMR 8256, INSERM ERL U1164, Biological Adaptation and Ageing, Sorbonne Université, 75005 Paris, France
2
INSERM UMR-S 1180, Signalling and Cardiovascular Pathophysiology, Université Paris-Saclay, 92296 Châtenay-Malabry, France
*
Author to whom correspondence should be addressed.
Academic Editor: Andrea Disanza
Int. J. Mol. Sci. 2022, 23(13), 7394; https://doi.org/10.3390/ijms23137394
Received: 20 June 2022 / Accepted: 29 June 2022 / Published: 2 July 2022
(This article belongs to the Section Molecular Biology)
Myocardin-related transcription factors (MRTFs) play a central role in the regulation of actin expression and cytoskeletal dynamics that are controlled by Rho GTPases. SRF is a ubiquitous transcription factor strongly expressed in muscular tissues. The depletion of SRF in the adult mouse heart leads to severe dilated cardiomyopathy associated with the down-regulation of target genes encoding sarcomeric proteins including α-cardiac actin. The regulatory triad, composed of SRF, its cofactor MRTFA and actin, plays a major role in the coordination of the nuclear transcriptional response to adapt actin filament dynamics associated with changes in cell shape, and contractile and migratory activities. Most of the knowledge on the regulation of the SRF–MRTF–Actin axis has been obtained in non-muscle cells with α-actin and smooth muscle cells with α-smooth actin. Here, we visualized for the first time by a time-lapse video, the nucleocytoplasmic shuttling of MRTFA induced by serum or pro-hypertrophic agonists such as angiotensin II, phenylephrine and endothelin-1, using an MRTFA-GFP adenovirus in cultures of neonatal rat cardiomyocytes. We showed that an inhibitor of the RhoA/ROCK signaling pathway leads to an α-cardiac actin polymerization disruption and inhibition of MRTFA nucleocytoplasmic shuttling. Moreover, inhibition of the PI3K/Akt signaling pathway also prevents the entry of MRTFA into the nuclei. Our findings point out a central role of the SRF–MRTFA–actin axis in cardiac remodeling. View Full-Text
Keywords: MRTFA; nucleocytoplasmic shuttle; α-cardiac actin; SRF; RhoA/ROCK signaling pathway; polymerization; PI3K/Akt signaling pathway MRTFA; nucleocytoplasmic shuttle; α-cardiac actin; SRF; RhoA/ROCK signaling pathway; polymerization; PI3K/Akt signaling pathway
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MDPI and ACS Style

Gorey, M.-A.; Mericskay, M.; Li, Z.; Decaux, J.-F. Interrelation between α-Cardiac Actin Treadmilling and Myocardin-Related Transcription Factor-A Nuclear Shuttling in Cardiomyocytes. Int. J. Mol. Sci. 2022, 23, 7394. https://doi.org/10.3390/ijms23137394

AMA Style

Gorey M-A, Mericskay M, Li Z, Decaux J-F. Interrelation between α-Cardiac Actin Treadmilling and Myocardin-Related Transcription Factor-A Nuclear Shuttling in Cardiomyocytes. International Journal of Molecular Sciences. 2022; 23(13):7394. https://doi.org/10.3390/ijms23137394

Chicago/Turabian Style

Gorey, Mark-Alexander, Mathias Mericskay, Zhenlin Li, and Jean-François Decaux. 2022. "Interrelation between α-Cardiac Actin Treadmilling and Myocardin-Related Transcription Factor-A Nuclear Shuttling in Cardiomyocytes" International Journal of Molecular Sciences 23, no. 13: 7394. https://doi.org/10.3390/ijms23137394

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