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The mechanical stability of proteins regulates their translocation rate into the cell nucleus

Research output: Contribution to journalArticle

Elvira Infante, Andrew Stannard, Stephanie J. Board, Palma Rico-Lastres, Elena Rostkova, Amy E.M. Beedle, Ainhoa Lezamiz, Yong Jian Wang, Samuel Gulaidi Breen, Fani Panagaki, Vinoth Sundar Rajan, Catherine Shanahan, Pere Roca-Cusachs, Sergi Garcia-Manyes

Original languageEnglish
Pages (from-to)973-981
Number of pages9
JournalNature Physics
Volume15
Issue number9
Early online date1 Jul 2019
DOIs
Publication statusPublished - 1 Sep 2019

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Abstract

A cell’s ability to react to mechanical stimuli is known to be affected by the transport of transcription factors, the proteins responsible for regulating transcription of DNA into RNA, across the membrane enveloping its nucleus. Yet the molecular mechanisms by which mechanical cues control this process remain unclear. Here we show that one such protein, myocardin-related transcription factor A (MRTFA), is imported into the nucleus at a rate that is inversely correlated with its nanomechanical stability, but independent of its thermodynamic stability. Attaching mechanically stable proteins to MRTFA results in reduced gene expression and the subsequent slowing down of cell migration. We conclude that the mechanical unfolding of proteins regulates their nuclear translocation rate, and highlight the role of the nuclear pore complex as a selective mechanosensor that is capable of detecting forces as low as ∼10 pN. The modulation of the mechanical stability of transcription factors may represent a general strategy for the control of gene expression.

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