Mechanotransduction at the Nuclear Envelope

LINC complexes are transmembrane protein assemblies that physically connect the nucleo- and cytoskeletons through the nuclear envelope. Dysfunctions of LINC complexes are associated with pathologies such as cancer and muscular dystrophies. The mechanical roles of LINC complex proteins in these contexts are poorly understood. To address this issue, we have developed genetically encoded FRET biosensors that measure molecular tension in LINC complex proteins.We have evidenced that LINC complex proteins are under tension generated by the cytoskeleton and sensitive to various external and internal mechanical constraints in fibroblastic and epithelial cells. In addition, we have shown that some of the same constraints result in the localization at the nuclear envelope of alpha-catenin, an actin- binding protein required for intercellular adhesion that can also act as a transcription regulator. These results are consistent with a mechanotransduction activity of LINC complex proteins, the targets of which we currently investigate.