Cofilin-1 Is a mechanosensitive regulator of transcription

Catarina Domingues, A. Margarida Geraldo, Sandra Isabel Anjo, André Matos, Cláudio Almeida, Inês Caramelo, José A. Lopes-da-Silva, Artur Paiva, João Carvalho, Ricardo Pires das Neves, Bruno Manadas*, Mário Grãos

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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.
Original languageEnglish
Article number678
JournalFrontiers in Cell and Developmental Biology
Volume8
DOIs
Publication statusPublished - 30 Jul 2020
Externally publishedYes

Keywords

  • Cofilin-1
  • Cytoskeleton
  • hUCM-MSCs
  • Mechanotransduction
  • Proteomics
  • Transcription

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