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Title: Cofilin-1 Is a Mechanosensitive Regulator of Transcription
Authors: Domingues, Catarina 
Geraldo, A. Margarida 
Anjo, Sandra I. 
Matos, André 
Almeida, Cláudio 
Caramelo, Inês 
Lopes-da-Silva, José A
Paiva, Artur 
Carvalho, João 
Neves, Ricardo Pires das 
Manadas, Bruno 
Grãos, Mário 
Keywords: mechanotransduction; Cofilin-1; cytoskeleton; transcription; hUCM-MSCs; proteomics
Issue Date: 2020
Publisher: Frontiers Media S.A.
Project: POCI-01- 0145-FEDER-029516 
Serial title, monograph or event: Frontiers in Cell and Developmental Biology
Volume: 8
Abstract: 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.
ISSN: 2296-634X
DOI: 10.3389/fcell.2020.00678
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
IIIUC - Artigos em Revistas Internacionais
I&D ICBR - Artigos em Revistas Internacionais
I&D CIBB - Artigos em Revistas Internacionais
I&D CFis - Artigos em Revistas Internacionais
I&D CFis - Artigos em Revistas Internacionais

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