Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/56221 |
Resumo: | Centre de recherche en Myologie, U974 SU-INSERM, 75013 Paris, France. |
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Le Dour, CarolineChatzifrangkeskou, MariaMacquart, ColineMagiera, Maria M.Peccate, CécileJouve, CharlèneVirtanen, LauraHeliö, TinaAalto-Setälä, KatriinaCrasto, SilviaCadot, BrunoCardoso, DéborahMougenot, NathalieAdesse, DanielDi Pasquale, ElisaHulot, Jean-SébastienTaimen, PekkaJanke, CarstenMuchir, Antoine2022-12-29T11:56:52Z2022-12-29T11:56:52Z2022LE DOUR, Caroline et al. Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations. Nature Comunications, v. 13, 7886, p. 1 - 21, 2022.2041-1723https://www.arca.fiocruz.br/handle/icict/5622110.1038/s41467-022-35639-xengNatureInteração actina-microtúbulos do citoesqueletoMediada pela sinalização MRTF-A/SRFPromove cardiomiopatia dilatadaCausada por mutações LMNAActin-microtubule cytoskeletal interplayMediated by MRTF-A/SRF signalingPromotes dilated cardiomyopathCaused by LMNA mutationsActin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutationsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleCentre de recherche en Myologie, U974 SU-INSERM, 75013 Paris, France.Centre de recherche en Myologie, U974 SU-INSERM, 75013 Paris, France.Centre de recherche en Myologie, U974 SU-INSERM, 75013 Paris, France.Institut Curie, Université PSL, CNRSUMR3348, 91401 Orsay, France / Université Paris-Saclay, CNRS UMR3348, 91401 Orsay, France.Centre de recherche en Myologie, U974 SU-INSERM, 75013 Paris, France.Université de Paris, Paris Cardiovascular Research Center PARCC, INSERM, 75015 Paris, France.Institute of Biomedicine and FICAN West Cancer Centre, University of Turku, 20520 Turku, Finland.Heart and Lung Centre, Helsinki University Central Hospital, University of Helsinki, 00290 Helsinki, Finland.Faculty of Medicine and Health Technology and BioMediTech Institute, Tampere University, 33520 Tampere, Finland.Institute of Genetic and Biomedical Research (IRGB), UOS of Milan, National Research Council of Italy, Milan, Italy / Humanitas Clinical and Research Center-IRCCS, 20089 Rozzano (MI), Italy.Centre de recherche en Myologie, U974 SU-INSERM, 75013 Paris, France.Centre de recherche en Myologie, U974 SU-INSERM, 75013 Paris, France.Sorbonne Université, INSERM, UMS28 Phénotypage du petit animal, Paris 75013, France.Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Biologia Estrutural, Rio de Janeiro, RJ, Brasil.Institute of Genetic and Biomedical Research (IRGB), UOS of Milan, National Research Council of Italy, Milan, Italy / Humanitas Clinical and Research Center-IRCCS, 20089 Rozzano (MI), Italy.Université de Paris, Paris Cardiovascular Research Center PARCC, INSERM, 75015 Paris, France.Institute of Biomedicine and FICAN West Cancer Centre, University of Turku, 20520 Turku, Finland / Department of Pathology, Turku University Hospital, 20520 Turku, Finland.Institut Curie, Université PSL, CNRSUMR3348, 91401 Orsay, France / Université Paris-Saclay, CNRS UMR3348, 91401 Orsay, France.Centre de recherche en Myologie, U974 SU-INSERM, 75013 Paris, France.Mutations in the lamin A/C gene (LMNA) cause dilated cardiomyopathy associated with increased activity of ERK1/2 in the heart. We recently showed that ERK1/2 phosphorylates cofilin-1 on threonine 25 (phospho(T25)-cofilin-1) that in turn disassembles the actin cytoskeleton. Here, we show that inmuscle cells carrying a cardiomyopathy-causing LMNA mutation, phospho(T25)-cofilin-1 binds to myocardin-related transcription factor A (MRTF-A) in the cytoplasm, thus preventing the stimulation of serumresponse factor (SRF) in the nucleus. Inhibiting the MRTF-A/SRF axis leads to decreased α-tubulin acetylation by reducing the expression of ATAT1 gene encoding α-tubulin acetyltransferase 1. Hence, tubulin acetylation is decreased in cardiomyocytes derived from male patients with LMNA mutations and in heart and isolated cardiomyocytes from Lmnap.H222P/H222P male mice. In Atat1 knockout mice, deficient for acetylated α- tubulin, we observe left ventricular dilation andmislocalization of Connexin 43 (Cx43) in heart. Increasing α-tubulin acetylation levels in Lmnap.H222P/H222P mice with tubastatin A treatment restores the proper localization of Cx43 and improves cardiac function. In summary, we show for the first time an actinmicrotubule cytoskeletal interplay mediated by cofilin-1 and MRTF-A/SRF, promoting the dilated cardiomyopathy caused by LMNA mutations. Our findings suggest that modulating α-tubulin acetylation levels is a feasible strategy for improving cardiac function.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/56221/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALDanielAdesse_etal_IOC_2022.pdfDanielAdesse_etal_IOC_2022.pdfapplication/pdf11854990https://www.arca.fiocruz.br/bitstream/icict/56221/2/DanielAdesse_etal_IOC_2022.pdfc262621f95331375ba3cc0712154e0d9MD52icict/562212023-09-04 11:03:18.602oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-09-04T14:03:18Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.en_US.fl_str_mv |
Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations |
| title |
Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations |
| spellingShingle |
Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations Le Dour, Caroline Interação actina-microtúbulos do citoesqueleto Mediada pela sinalização MRTF-A/SRF Promove cardiomiopatia dilatada Causada por mutações LMNA Actin-microtubule cytoskeletal interplay Mediated by MRTF-A/SRF signaling Promotes dilated cardiomyopath Caused by LMNA mutations |
| title_short |
Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations |
| title_full |
Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations |
| title_fullStr |
Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations |
| title_full_unstemmed |
Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations |
| title_sort |
Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations |
| author |
Le Dour, Caroline |
| author_facet |
Le Dour, Caroline Chatzifrangkeskou, Maria Macquart, Coline Magiera, Maria M. Peccate, Cécile Jouve, Charlène Virtanen, Laura Heliö, Tina Aalto-Setälä, Katriina Crasto, Silvia Cadot, Bruno Cardoso, Déborah Mougenot, Nathalie Adesse, Daniel Di Pasquale, Elisa Hulot, Jean-Sébastien Taimen, Pekka Janke, Carsten Muchir, Antoine |
| author_role |
author |
| author2 |
Chatzifrangkeskou, Maria Macquart, Coline Magiera, Maria M. Peccate, Cécile Jouve, Charlène Virtanen, Laura Heliö, Tina Aalto-Setälä, Katriina Crasto, Silvia Cadot, Bruno Cardoso, Déborah Mougenot, Nathalie Adesse, Daniel Di Pasquale, Elisa Hulot, Jean-Sébastien Taimen, Pekka Janke, Carsten Muchir, Antoine |
| author2_role |
author author author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Le Dour, Caroline Chatzifrangkeskou, Maria Macquart, Coline Magiera, Maria M. Peccate, Cécile Jouve, Charlène Virtanen, Laura Heliö, Tina Aalto-Setälä, Katriina Crasto, Silvia Cadot, Bruno Cardoso, Déborah Mougenot, Nathalie Adesse, Daniel Di Pasquale, Elisa Hulot, Jean-Sébastien Taimen, Pekka Janke, Carsten Muchir, Antoine |
| dc.subject.other.en_US.fl_str_mv |
Interação actina-microtúbulos do citoesqueleto Mediada pela sinalização MRTF-A/SRF Promove cardiomiopatia dilatada Causada por mutações LMNA |
| topic |
Interação actina-microtúbulos do citoesqueleto Mediada pela sinalização MRTF-A/SRF Promove cardiomiopatia dilatada Causada por mutações LMNA Actin-microtubule cytoskeletal interplay Mediated by MRTF-A/SRF signaling Promotes dilated cardiomyopath Caused by LMNA mutations |
| dc.subject.en.en_US.fl_str_mv |
Actin-microtubule cytoskeletal interplay Mediated by MRTF-A/SRF signaling Promotes dilated cardiomyopath Caused by LMNA mutations |
| description |
Centre de recherche en Myologie, U974 SU-INSERM, 75013 Paris, France. |
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2022 |
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2022-12-29T11:56:52Z |
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2022-12-29T11:56:52Z |
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2022 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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LE DOUR, Caroline et al. Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations. Nature Comunications, v. 13, 7886, p. 1 - 21, 2022. |
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https://www.arca.fiocruz.br/handle/icict/56221 |
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2041-1723 |
| dc.identifier.doi.none.fl_str_mv |
10.1038/s41467-022-35639-x |
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LE DOUR, Caroline et al. Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations. Nature Comunications, v. 13, 7886, p. 1 - 21, 2022. 2041-1723 10.1038/s41467-022-35639-x |
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