PT  - JOURNAL ARTICLE
AU  - Théophile Déjardin
AU  - Pietro Salvatore Carollo
AU  - Patricia M. Davidson
AU  - Cynthia Seiler
AU  - Damien Cuvelier
AU  - Bruno Cadot
AU  - Cecile Sykes
AU  - Edgar R. Gomes
AU  - Nicolas Borghi
TI  - LINC complexes are mechanotransducers that discriminate Epithelial-Mesenchymal Transition programs
AID  - 10.1101/744276
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 744276
4099  - http://biorxiv.org/content/early/2019/08/22/744276.short
4100  - http://biorxiv.org/content/early/2019/08/22/744276.full
AB  - 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 disorders. The mechanical roles of LINC complexes in these contexts are poorly understood. To address this, we used genetically encoded FRET biosensors of molecular tension in LINC complex proteins of fibroblastic and epithelial cells in culture. We exposed cells to mechanical, genetic and pharmacological perturbations, mimicking a range of physiological and pathological situations. We show that LINC complex proteins experience tension generated by the cytoskeleton and act as mechanical sensors of cell packing. Moreover, the LINC complex discriminates between inductions of partial and complete epithelial-mesenchymal transitions (EMT). We identify the implicated mechanisms, which associate nesprin tension sensing with α-catenin capture at the nuclear envelope, thereby regulating β-catenin transcription. Our data thus implicate that LINC complexes are mechanotransducers that fine-tune β-catenin signaling in a manner dependent on the Epithelial-Mesenchymal Transition program.