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Cofilin-1 Is a Mechanosensitive Regulator of Transcription

Authors: Domingues, C; Geraldo, AM; Anjo, SI; Matos, A; Almeida, C; Caramelo, I; Lopes-da-Silva, JA; Paiva, A; Carvalho, J; das Neves, RP; Manadas, B; Graos, M

Ref.: Front. Cell Dev. Biol. 8, 678 (2020)

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.

DOI: 10.3389/fcell.2020.00678