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

Takao Hikita, Fatemeh Mirzapourshafiyi, Pedro Barbacena, Meghan Riddell, Ayesha Pasha, Mengnan Li, Takuji Kawamura, Ralf P. Brandes, Tomonori Hirose, Shigeo Ohno, Holger Gerhardt, Michiyuki Matsuda, Claudio A. Franco, Masanori Nakayama

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

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.

Original languageEnglish
Article numbere45253
JournalEMBO Reports
Volume19
Issue number9
DOIs
Publication statusPublished - Sep 2018
Externally publishedYes

Keywords

  • atherosclerosis
  • cell polarity
  • endothelial cell
  • flow
  • PAR-3

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint

Dive into the research topics of 'PAR-3 controls endothelial planar polarity and vascular inflammation under laminar flow'. Together they form a unique fingerprint.

Cite this