TY - JOUR
T1 - The mechanical stability of proteins regulates their translocation rate into the cell nucleus
AU - Infante, Elvira
AU - Stannard, Andrew
AU - Board, Stephanie J.
AU - Rico-Lastres, Palma
AU - Rostkova, Elena
AU - Beedle, Amy E.M.
AU - Lezamiz, Ainhoa
AU - Wang, Yong Jian
AU - Gulaidi Breen, Samuel
AU - Panagaki, Fani
AU - Sundar Rajan, Vinoth
AU - Shanahan, Catherine
AU - Roca-Cusachs, Pere
AU - Garcia-Manyes, Sergi
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85068545228&partnerID=8YFLogxK
U2 - 10.1038/s41567-019-0551-3
DO - 10.1038/s41567-019-0551-3
M3 - Article
AN - SCOPUS:85068545228
SN - 1745-2473
VL - 15
SP - 973
EP - 981
JO - Nature Physics
JF - Nature Physics
IS - 9
ER -