The mechanical stability of proteins regulates their translocation rate into the cell nucleus
| Autor: | Elvira Infante, Yongjian Wang, Catherine M. Shanahan, Stephanie Board, Andrew Stannard, Samuel A. Gulaidi Breen, Ainhoa Lezamiz, Palma Rico-Lastres, Fani Panagaki, Vinoth Sundar Rajan, Elena Rostkova, Pere Roca-Cusachs, Sergi Garcia-Manyes, Amy E. M. Beedle |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Infante, E, Stannard, A, Board, S J, Rico-Lastres, P, Rostkova, E, Beedle, A E M, Lezamiz, A, Wang, Y J, Gulaidi Breen, S, Panagaki, F, Sundar Rajan, V, Shanahan, C, Roca-Cusachs, P & Garcia-Manyes, S 2019, ' The mechanical stability of proteins regulates their translocation rate into the cell nucleus ', Nature Physics, vol. 15, no. 9, pp. 973-981 . https://doi.org/10.1038/s41567-019-0551-3 Publons Nature Physics |
| DOI: | 10.1038/s41567-019-0551-3 |
| Popis: | 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. The rate at which proteins are imported into the nucleus of a cell is shown to be regulated by their mechanical unfolding, a mechanism that identifies the nuclear pore machinery as a highly sensitive force detector. |
| Databáze: | OpenAIRE |
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