Nesprin-1 Is Required for Endothelial Cell Polarization, Motility and Mechanotransduction

Endothelial cell (EC) polarization and directional migration is required for angiogenesis. Polarization and motility requires not only local cytoskeletal remodeling but also the motion of intracellular organelles. In particular, positioning of the nucleus is an important part of any dynamic change in cell morphology; however, the physiological significance of nuclear positioning in the endothelial cell has remained unexplored. Here, we show that siRNA knockdown of nesprin-1, a protein present in the LINC complex (linker of nucleus to cytoskeleton), abolished the reorientation of endothelial cells in response to cyclic strain. Further, knockdown of nesprin-1 significantly inhibited EC migration in a scratch-wound assay and caused defective single-cell motility. Cell polarization assays showed that nesprin-1 depletion caused defects in nuclear positioning. Taken together, these results suggest that nesprin-1 is required for endothelial polarization, motility and mechanotransduction.