{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T14:15:11Z","timestamp":1771337711374,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T00:00:00Z","timestamp":1656720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"l\u2019Association Fran\u00e7aise contre les Myopathies","award":["AFM#19814"],"award-info":[{"award-number":["AFM#19814"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u03b1-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\u2013MRTF\u2013Actin axis has been obtained in non-muscle cells with \u03b1-actin and smooth muscle cells with \u03b1-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 \u03b1-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\u2013MRTFA\u2013actin axis in cardiac remodeling.<\/jats:p>","DOI":"10.3390\/ijms23137394","type":"journal-article","created":{"date-parts":[[2022,7,3]],"date-time":"2022-07-03T22:50:46Z","timestamp":1656888646000},"page":"7394","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Interrelation between \u03b1-Cardiac Actin Treadmilling and Myocardin-Related Transcription Factor-A Nuclear Shuttling in Cardiomyocytes"],"prefix":"10.3390","volume":"23","author":[{"given":"Mark-Alexander","family":"Gorey","sequence":"first","affiliation":[{"name":"Institut de Biologie Paris-Seine (IBPS), CNRS UMR 8256, INSERM ERL U1164, Biological Adaptation and Ageing, Sorbonne Universit\u00e9, 75005 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6779-092X","authenticated-orcid":false,"given":"Mathias","family":"Mericskay","sequence":"additional","affiliation":[{"name":"INSERM UMR-S 1180, Signalling and Cardiovascular Pathophysiology, Universit\u00e9 Paris-Saclay, 92296 Ch\u00e2tenay-Malabry, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3706-4505","authenticated-orcid":false,"given":"Zhenlin","family":"Li","sequence":"additional","affiliation":[{"name":"Institut de Biologie Paris-Seine (IBPS), CNRS UMR 8256, INSERM ERL U1164, Biological Adaptation and Ageing, Sorbonne Universit\u00e9, 75005 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Fran\u00e7ois","family":"Decaux","sequence":"additional","affiliation":[{"name":"Institut de Biologie Paris-Seine (IBPS), CNRS UMR 8256, INSERM ERL U1164, Biological Adaptation and Ageing, Sorbonne Universit\u00e9, 75005 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.1161\/CIRCULATIONAHA.105.533778","article-title":"Temporally controlled onset of dilated cardiomyopathy through disruption of the SRF gene in adult heart","volume":"112","author":"Parlakian","year":"2005","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"40033","DOI":"10.1074\/jbc.M104934200","article-title":"Early postnatal cardiac changes and premature death in transgenic mice overexpressing a mutant form of serum response factor","volume":"276","author":"Zhang","year":"2001","journal-title":"J. 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