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

EMBO Reports
Takao HikitaMasanori Nakayama

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.

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Citations

Jul 19, 2019·Circulation Research·Petya B GeorgievaUNKNOWN Leducq ATTRACT Consortium*
Feb 20, 2020·Journal of Cardiovascular Translational Research·Marc P Wolf, Patrick Hunziker
Dec 30, 2020·International Journal of Molecular Sciences·Lei Wang, Chaojun Tang
Mar 4, 2021·Current Opinion in Hematology·Andreia PenaCláudio Areias Franco
Jun 17, 2021·PLoS Computational Biology·Fatemeh Mirzapour-ShafiyiMasanori Nakayama
Aug 3, 2021·The Plant Cell·João Jacob RamalhoDolf Weijers
Aug 24, 2021·Cells & Development·Marie OuarnéCláudio Areias Franco

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