Nesprins are mechanotransducers that discriminate epithelial–mesenchymal transition programs

LINC complexes are assemblies of transmembrane proteins that physically link the nucleoskeleton and cytoskeleton through the nuclear envelope. Dysfunctions of LINC complexes are associated with cancer and muscle pathologies. The mechanical roles of LINC complexes in these diseases are poorly understood. To remedy this, an IJM team has used FRET molecular tension biosensors genetically encoded in nesprin, a protein of the LINC complex, in fibroblast and epithelial cells in culture.

The team exposed the cells to mechanical, genetic and pharmacological perturbations mimicking a range of physiological and pathological situations to show that nesprin undergoes cytoskeletal-generated stress and acts as a mechanical sensor of cell density. In addition, nesprin is able to distinguish between the induction of partial and complete epithelium-mesenchyme transitions. The mechanisms identified involve the capture of α-catenin at the nuclear envelope by nesprin upon its relaxation, thereby regulating the transcriptional activity of β-catenin. These data therefore involve the proteins of the LINC complex as mechanosensitive regulators of the β-catenin pathway in a manner dependent on the epithelium-mesenchyme transition program.

To know more: Nesprins are mechanotransducers that discriminate epithelial-mesenchymal transition programs. Déjardin T, Carollo PS, Sipieter F, Davidson PM, Seiler C, Cuvelier D, Cadot B, Sykes C, Gomes ER,Borghi N. J Cell Biol. 2020 Oct 5;219(10):e201908036. doi: 10.1083/jcb.201908036

Spotlight: Nesprin-2G tension fine-tunes Wnt/β-catenin signaling. Cara J. Gottardi, G.W. Gant Luxton. J Cell Biol (2020) 219 (10): e202009042. doi:10.1083/jcb.202009042

contact: nicolas.borghi(at)ijm.fr

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