| First Author | Hikita T | Year | 2018 |
| Journal | EMBO Rep | Volume | 19 |
| Issue | 9 | PubMed ID | 30018153 |
| Mgi Jnum | J:265192 | Mgi Id | MGI:6199242 |
| Doi | 10.15252/embr.201745253 | Citation | Hikita T, et al. (2018) PAR-3 controls endothelial planar polarity and vascular inflammation under laminar flow. EMBO Rep 19(9) |
| abstractText | Impaired cell polarity is a hallmark of diseased tissue. In the cardiovascular system, laminar blood flow induces endothelial planar cell polarity, represented by elongated cell shape and asymmetric distribution of intracellular organelles along the axis of blood flow. Disrupted endothelial planar polarity is considered to be pro-inflammatory, suggesting that the establishment of endothelial polarity elicits an anti-inflammatory response. However, a causative relationship between polarity and inflammatory responses has not been firmly established. Here, we find that a cell polarity protein, PAR-3, is an essential gatekeeper of GSK3beta activity in response to laminar blood flow. We show that flow-induced spatial distribution of PAR-3/aPKClambda and aPKClambda/GSK3beta complexes controls local GSK3beta activity and thereby regulates endothelial planar polarity. The spatial information for GSK3beta activation is essential for flow-dependent polarity to the flow axis, but is not necessary for flow-induced anti-inflammatory response. Our results shed light on a novel relationship between endothelial polarity and vascular homeostasis highlighting avenues for novel therapeutic strategies. |
