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.
journal_name
Circ Resjournal_title
Circulation researchauthors
McCue S,Dajnowiec D,Xu F,Zhang M,Jackson MR,Langille BLdoi
10.1161/01.RES.0000216595.15868.55subject
Has Abstractpub_date
2006-04-14 00:00:00pages
939-46issue
7eissn
0009-7330issn
1524-4571pii
01.RES.0000216595.15868.55journal_volume
98pub_type
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