Speaker: Sergi Garcia-Manyes
Professor of Physics and Structural Biology, Head of Group, King’s College, London
Title: The mechanical stability of proteins regulates their translocation rate into the cell nucleus
Abstract: The translocation of mechanosensitive transcription factors (TFs) across the nuclear envelope is a crucial step in cellular mechanotransduction. Yet the molecular mechanisms by which mechanical cues control the nuclear shuttling dynamics of TFs through the nuclear pore complex (NPC) to activate gene expression are poorly understood. Here, we show that the nuclear import rate of myocardin-related transcription factor A (MRTFA) — a protein that regulates cytoskeletal dynamics via the activation of the TF serum response factor (SRF) — inversely correlates with the protein’s nanomechanical stability and does not relate to its thermodynamic stability. Tagging MRTFA with mechanically stable proteins results in the downregulation of SRF-mediated gene expression and subsequent slowing down of cell migration. We conclude that the mechanical unfolding of proteins regulates their nuclear translocation rate through the NPC and highlight the role of the NPC as a selective mechanosensor able to discriminate forces as low as ~10 pN. The modulation of the mechanical stability of TFs may represent a new, general strategy for the control of gene expression.
Speaker’s Bio: Sergi graduated in chemistry from the University of Barcelona (2000) and obtained his Ph.D. in Physical Chemistry from the same university, working on Scanning Probe Microscopy techniques. He then moved to New York to conduct his postdoctoral training in the field of single-molecule mechanics in the Biology Department of Columbia University with Julio Fernández.
In 2011 he moved to the UK, where he established his laboratory at King’s College London, in a joint appointment between the Department of Physics and the Randall Division of Cell and Molecular Biophysics. In 2016 he was appointed Professor of Biophysics. He is the Director of two Centres for doctoral training, one on Biological Physics and the other one on Mechanobiology funded by the Leverhulme Trust.
Since 2017 he is the Head of the Biological Physics and Soft Matter research group in the Physics Department of King’s. From 2020 he is a group leader at the Francis Crick Institute.
Sergi’s laboratory aims to understand the molecular mechanisms that govern cellular mechanobiology.
Sergi held an EPSRC Early Career Fellowship and holds a Leverhulme Research Leadership Award and a Wellcome Trust Investigator Award. He is a Royal Society Wolfson Fellow.
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Meeting ID: 962 2795 7366 Passcode: D4oAX17B