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PAR-3 controls endothelial planar polarity and vascular inflammation under laminar flow

Item Type:Article
Title:PAR-3 controls endothelial planar polarity and vascular inflammation under laminar flow
Creators Name:Hikita, T. and Mirzapourshafiyi, F. and Barbacena, P. and Riddell, M. and Pasha, A. and Li, M. and Kawamura, T. and Brandes, R.P. and Hirose, T. and Ohno, S. and Gerhardt, H. and Matsuda, M. and Franco, C.A. and Nakayama, M.
Abstract: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 GSK3β activity in response to laminar blood flow. We show that flow-induced spatial distribution of PAR-3/aPKCλ and aPKCλ/GSK3β complexes controls local GSK3β activity and thereby regulates endothelial planar polarity. The spatial information for GSK3β 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.
Keywords:Atherosclerosis, Cell Polarity, Endothelial Cell, Flow, PAR-3, Animals, Mice
Source:EMBO Reports
Publisher:EMBO Press / Wiley
Page Range:e45253
Date:1 September 2018
Official Publication:https://doi.org/10.15252/embr.201745253
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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