Cofilin-1 is a mechanosensitive regulator of transcription
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10773/30552 |
Resumo: | The mechanical properties of the extracellular environment are interrogated by cells and integrated through mechanotransduction. Many cellular processes depend on actomyosin-dependent contractility, which is influenced by the microenvironment's stiffness. Here, we explored the influence of substrate stiffness on the proteome of proliferating undifferentiated human umbilical cord-matrix mesenchymal stem/stromal cells. The relative abundance of several proteins changed significantly by expanding cells on soft (∼3 kPa) or stiff substrates (GPa). Many such proteins are associated with the regulation of the actin cytoskeleton, a major player of mechanotransduction and cell physiology in response to mechanical cues. Specifically, Cofilin-1 levels were elevated in cells cultured on soft comparing with stiff substrates. Furthermore, Cofilin-1 was de-phosphorylated (active) and present in the nuclei of cells kept on soft substrates, in contrast with phosphorylated (inactive) and widespread distribution in cells on stiff. Soft substrates promoted Cofilin-1-dependent increased RNA transcription and faster RNA polymerase II-mediated transcription elongation. Cofilin-1 is part of a novel mechanism linking mechanotransduction and transcription. |
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Cofilin-1 is a mechanosensitive regulator of transcriptionMechanotransductionCofilin-1CytoskeletonTranscriptionhUCM-MSCsProteomicsThe mechanical properties of the extracellular environment are interrogated by cells and integrated through mechanotransduction. Many cellular processes depend on actomyosin-dependent contractility, which is influenced by the microenvironment's stiffness. Here, we explored the influence of substrate stiffness on the proteome of proliferating undifferentiated human umbilical cord-matrix mesenchymal stem/stromal cells. The relative abundance of several proteins changed significantly by expanding cells on soft (∼3 kPa) or stiff substrates (GPa). Many such proteins are associated with the regulation of the actin cytoskeleton, a major player of mechanotransduction and cell physiology in response to mechanical cues. Specifically, Cofilin-1 levels were elevated in cells cultured on soft comparing with stiff substrates. Furthermore, Cofilin-1 was de-phosphorylated (active) and present in the nuclei of cells kept on soft substrates, in contrast with phosphorylated (inactive) and widespread distribution in cells on stiff. Soft substrates promoted Cofilin-1-dependent increased RNA transcription and faster RNA polymerase II-mediated transcription elongation. Cofilin-1 is part of a novel mechanism linking mechanotransduction and transcription.Frontiers Media S.A.2021-02-11T11:48:34Z2020-07-30T00:00:00Z2020-07-30info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10773/30552eng10.3389/fcell.2020.00678Domingues, CatarinaGeraldo, A MargaridaAnjo, Sandra IsabelMatos, AndréAlmeida, CláudioCaramelo, InêsLopes-da-Silva, José APaiva, ArturCarvalho, JoãoPires das Neves, RicardoManadas, BrunoGrãos, Márioinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T11:59:04Zoai:ria.ua.pt:10773/30552Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:02:38.047007Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Cofilin-1 is a mechanosensitive regulator of transcription |
title |
Cofilin-1 is a mechanosensitive regulator of transcription |
spellingShingle |
Cofilin-1 is a mechanosensitive regulator of transcription Domingues, Catarina Mechanotransduction Cofilin-1 Cytoskeleton Transcription hUCM-MSCs Proteomics |
title_short |
Cofilin-1 is a mechanosensitive regulator of transcription |
title_full |
Cofilin-1 is a mechanosensitive regulator of transcription |
title_fullStr |
Cofilin-1 is a mechanosensitive regulator of transcription |
title_full_unstemmed |
Cofilin-1 is a mechanosensitive regulator of transcription |
title_sort |
Cofilin-1 is a mechanosensitive regulator of transcription |
author |
Domingues, Catarina |
author_facet |
Domingues, Catarina Geraldo, A Margarida Anjo, Sandra Isabel Matos, André Almeida, Cláudio Caramelo, Inês Lopes-da-Silva, José A Paiva, Artur Carvalho, João Pires das Neves, Ricardo Manadas, Bruno Grãos, Mário |
author_role |
author |
author2 |
Geraldo, A Margarida Anjo, Sandra Isabel Matos, André Almeida, Cláudio Caramelo, Inês Lopes-da-Silva, José A Paiva, Artur Carvalho, João Pires das Neves, Ricardo Manadas, Bruno Grãos, Mário |
author2_role |
author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Domingues, Catarina Geraldo, A Margarida Anjo, Sandra Isabel Matos, André Almeida, Cláudio Caramelo, Inês Lopes-da-Silva, José A Paiva, Artur Carvalho, João Pires das Neves, Ricardo Manadas, Bruno Grãos, Mário |
dc.subject.por.fl_str_mv |
Mechanotransduction Cofilin-1 Cytoskeleton Transcription hUCM-MSCs Proteomics |
topic |
Mechanotransduction Cofilin-1 Cytoskeleton Transcription hUCM-MSCs Proteomics |
description |
The mechanical properties of the extracellular environment are interrogated by cells and integrated through mechanotransduction. Many cellular processes depend on actomyosin-dependent contractility, which is influenced by the microenvironment's stiffness. Here, we explored the influence of substrate stiffness on the proteome of proliferating undifferentiated human umbilical cord-matrix mesenchymal stem/stromal cells. The relative abundance of several proteins changed significantly by expanding cells on soft (∼3 kPa) or stiff substrates (GPa). Many such proteins are associated with the regulation of the actin cytoskeleton, a major player of mechanotransduction and cell physiology in response to mechanical cues. Specifically, Cofilin-1 levels were elevated in cells cultured on soft comparing with stiff substrates. Furthermore, Cofilin-1 was de-phosphorylated (active) and present in the nuclei of cells kept on soft substrates, in contrast with phosphorylated (inactive) and widespread distribution in cells on stiff. Soft substrates promoted Cofilin-1-dependent increased RNA transcription and faster RNA polymerase II-mediated transcription elongation. Cofilin-1 is part of a novel mechanism linking mechanotransduction and transcription. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-07-30T00:00:00Z 2020-07-30 2021-02-11T11:48:34Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10773/30552 |
url |
http://hdl.handle.net/10773/30552 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.3389/fcell.2020.00678 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Frontiers Media S.A. |
publisher.none.fl_str_mv |
Frontiers Media S.A. |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799137681725194240 |