Nesprin‐1 and nesprin‐2 regulate endothelial cell shape and migration

Abstract

Nesprins are large multi-domain proteins that link the nuclear envelope to the cytoskeleton and nucleoskeleton. Here we show that nesprin-1 and nesprin-2 play important roles in regulating cell shape and migration in endothelial cells. Nesprin-1 or nesprin-2 depletion by RNAi increased endothelial cell spread area and the length of cellular protrusions, as well as stimulating stress fibre assembly which correlated with an increase in F-actin levels. Nuclear area was also increased by nesprin depletion, and localization of the inner nuclear membrane protein emerin to the nuclear envelope was reduced. Depletion of nesprin-1 or nesprin-2 reduced migration of endothelial cells into a cell-free area, and decreased loop formation in an in vitro angiogenesis assay. Taken together, our results indicate that nesprin-1 and nesprin-2 both regulate nuclear and cytoplasmic architecture, which we propose leads to their effects on endothelial cell migration and angiogenic loop formation.

Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes

“…Endothelium cells' capillary tube formation is correlated with a cascade downstream of integrin ligation induced by cell matrix interaction (Davis & Senger, ; Davis, Kon, & Stratman, ). Nesprins are proteins that link the cell nuclei to the cytoskeleton and are associated with the HUVECs' loop formation during angiogenesis (King et al, ). We speculate that Si 4+ can have some effect on the cell matrix interaction and/or nesprin activation and expression, and further investigation is necessary for clarification.…”

X‐ray‐enhanced cancer cell migration requires the linker of nucleoskeleton and cytoskeleton complex

“…Nesprins interact with the cytoskeleton, including actin filaments, intermediate filaments and microtubule motors; therefore, the LINC complex directly connects the nuclear interior to cytoskeleton. LINC complex and nuclear lamins form a solid scaffold for diverse functions, including nuclear migration, nuclear shaping and positioning, maintaining the centrosome‐nucleus connection, mechanotransduction, DNA repair, nuclear membrane spacing, cell migration, and moving chromosomes within the nucleus during meiosis …”

Drosophila KASH-domain protein Klarsicht regulates microtubule stability and integrin receptor localization during collective cell migration

“…Thus, we know little of how MTs and their associated proteins regulate such complex processes as the collective cell movements that occur during embryogenesis. Mammalian nesprin proteins have been shown to regulate the migration of a number of cell types, such as keratinocytes and endothelial cells (King et al, 2014; Rashmi et al, 2012); however, their control of cell migration is thought to occur through regulation of the actin cytoskeleton. Our studies provide the first evidence for a non-nuclear role of KASH-containing Klar in controlling cell migration through regulation of the MT cytoskeleton.…”

“…In support of a role for KASH domain proteins in cell migration, mammalian Nesprin-2 controls keratinocyte migration during wound healing, and Nesprin-1 and Nesprin-2 regulate endothelial cell shape and migration (King et al, 2014; Rashmi et al, 2012). This role of Nesprins in cell migration is attributed to their effects on actin polymerization and stress fiber assembly.…”