title: 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.
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL, United Kingdom; Cardiovascular Division and British Heart Foundation Centre of Research Excellence, King's College London, James Black Centre, Denmark Hill Campus, London, SE5 9NU, United Kingdom.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: King
authors.forename: Karolin
authors.initials: K
authors.lastname: Nowak
authors.forename: Narendra
authors.initials: N
authors.lastname: Suryavanshi
authors.forename: Ian
authors.initials: I
authors.lastname: Holt
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Shanahan
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Ridley
mesh_terms: D000199:Actins / Q000378:metabolism; D002465:Cell Movement; D048430:Cell Shape; D003598:Cytoskeletal Proteins; D005091:Exons / Q000235:genetics; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C415465:SYNE1 protein, human; C485904:SYNE2 protein, human; C092710:emerin
keywords: actin cytoskeleton; angiogenesis; cell migration; cell morphology; endothelial cells; nuclear envelope