Mechanotransduction in talin through the interaction of the R8 domain with DLC1

PLoS Biology
Alexander William M HainingArmando Del Río Hernández

Abstract

The mechanical unfolding of proteins is a cellular mechanism for force transduction with potentially broad implications in cell fate. Despite this, the mechanism by which protein unfolding elicits differential downstream signalling pathways remains poorly understood. Here, we used protein engineering, atomic force microscopy, and biophysical tools to delineate how protein unfolding controls cell mechanics. Deleted in liver cancer 1 (DLC1) is a negative regulator of Ras homolog family member A (RhoA) and cell contractility that regulates cell behaviour when localised to focal adhesions bound to folded talin. Using a talin mutant resistant to force-induced unfolding of R8 domain, we show that talin unfolding determines DLC1 downstream signalling and, consequently, cell mechanics. We propose that this new mechanism of mechanotransduction may have implications for a wide variety of associated cellular processes.

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Citations

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Methods Mentioned

BETA
GTPases
atomic force microscopy
fluorescent
recovery after photobleaching
electrophoresis
FRET

Software Mentioned

MTrackJ
PyMOL
Igor Pro ( Wavemetrics
MATLAB
GraphPad
smAFM
Gromacs
ImageJ
Prism

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