title: Shear stress regulates forward and reverse planar cell polarity of vascular endothelium in vivo and in vitro.
abstract: Cultured vascular endothelium displays profound morphological adaptations to shear stress that include planar cell polarity (PCP) that is directed downstream. Endothelial cells in blood vessels are also polarized; however, the direction of polarity is vessel specific, and shear-independent mechanisms have been inferred. The regulation of endothelial PCP is therefore controversial. We report that the direction of PCP in blood vessels is age and vessel specific; nonetheless, it is caused by shear-related regulation of glycogen synthase kinase-3beta (GSK-3beta), a profound regulator of endothelial microtubule stability. When GSK-3beta is inhibited, PCP reverses direction. Endothelium is the only cell type studied to date that can reverse direction of polarity. Tight regulation of GSK-3beta, microtubule dynamics, and cell polarity was also required for the striking morphological responses of endothelium to shear stress (cell elongation and orientation with shear). Finally, the cytoskeletal polarity displayed in blood vessels is associated with polarized (shear-directed) cell mitoses that have important effects on endothelial repair. Vascular endothelium therefore displays a novel mode of mechanosensitive PCP that represents the first example of a single cell type that can reverse direction of polarity.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Canada.
authors.forename: Shannon
authors.initials: S
authors.lastname: McCue
authors.forename: Dorota
authors.initials: D
authors.lastname: Dajnowiec
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Moira R
authors.initials: MR
authors.lastname: Jackson
authors.forename: B Lowell
authors.initials: BL
authors.lastname: Langille
mesh_terms: D000107:Acetylation; D000818:Animals; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D008870:Microtubules / Q000502:physiology; D011817:Rabbits; D013314:Stress, Mechanical; D013552:Swine; D014404:Tubulin / Q000378:metabolism
chemical_list: D014404:Tubulin; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3