Role of the nuclear membrane protein Emerin in front-rear polarity of the nucleus

Abstract

Cell polarity refers to the intrinsic asymmetry of cells, including the orientation of the cytoskeleton. It affects cell shape and structure as well as the distribution of proteins and organelles. In migratory cells, front-rear polarity is essential and dictates movement direction. While the link between the cytoskeleton and nucleus is well-studied, we aim to investigate if front-rear polarity can be transmitted to the nucleus. We show that the knock-down of emerin, an integral protein of the nuclear envelope, abolishes preferential localization of several nuclear proteins. We propose that the frontally biased localization of the endoplasmic reticulum, through which emerin reaches the nuclear envelope, is sufficient to generate its observed bias. In primary emerin-deficient myoblasts, its expression partially rescues the polarity of the nucleus. Our results demonstrate that front-rear cell polarity is transmitted to the nucleus and that emerin is an important determinant of nuclear polarity.

Mechanical and Physical Regulation of Fibroblast–Myofibroblast Transition: From Cellular Mechanoresponse to Tissue Pathology

“…Therefore, rearrangement of the cytoskeleton through mechanotransductive machinery leads to changes in the nucleus polarity and positioning within the cell, influencing cell migration (Vassaux et al, 2019;Moure and Gomez, 2020). Indeed, both F-actin and focal adhesion distributions were strongly influenced by this repositioning of nuclear compartment (Nastały et al, 2020). These findings provide intriguing insights that physical reorganization of the intracellular structural components and mechanotransductive players, which can be induced by changes in the tissue morphology, can directly affect FMT.…”

“…Depending on the abundance of its components, the ECM can present different microarchitectures, leading to different mechanical and physical properties. Importantly, interactions between the cells and the different ECM components can directly regulate cell behavior such as migration and development (Park et al, 2018;Changede et al, 2019;Nastały et al, 2020).…”

“…At the same time, the cell contractility is enhanced, causing the cell to release latent TGF-β and pushing toward FMT. Thus, dynamic interplay between the cells and the ECM induces cytoskeletal rearrangements that will simultaneously cause changes in the force transmission, cytoskeletal organization, and mechanical properties of the cell and its nucleus, as well as of the ECM in tissues (Jaalouk and Lammerding, 2009;Kurniawan et al, 2016;Nastały et al, 2020).…”

“…Indeed, fibroblasts exhibit differing functional identities, including the composition and expression profile of the intracellular macromolecules, depending on the tissue where they reside (Lynch and Watt, 2018;LeBleu and Neilson, 2020). In-vitro culture entails loss of most of mechanical and physical stimuli normally present in the tissue-specific microenvironments (Lynch and Watt, 2018), which affect not only the mechanical properties of the cells, but also cellular functions such as polarization (Nastały et al, 2020). This suggests a possible involvement of mechanotransduction in the regulation of gene expressions.…”

Tailoring Cellular Function: The Contribution of the Nucleus in Mechanotransduction

“…It was reported to be enriched at the ONM under cyclic strain stress ( Le et al, 2016 ), whereas Emerin-deficient cells showed impaired expression of mechanosensitive genes in response to strain ( Lammerding et al, 2005 ). Emerin has also been recently shown to be associated with nuclear stiffening and to be involved in maintaining nuclear front–rear polarity ( Nastały et al, 2020 ). Mutations in Emerin-encoding gene ( EMD ) cause X-linked EDMD that is associated with progressive muscle wasting and weakness followed by cardiac disease with conduction defects and arrhythmias ( Helbling-Leclerc et al, 2002 ).…”