Gpr124 Controls CNS Angiogenesis and Blood-Brain Barrier Integrity by Promoting Ligand-Specific Canonical Wnt Signaling

被引：207

作者：

Zhou, Yulian ^{[1
]}

Nathans, Jeremy ^{[1
,2
,3
,4
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA

来源：

DEVELOPMENTAL CELL | 2014年 / 31卷 / 02期

关键词：

RETINAL VASCULAR DEVELOPMENT; PROTEIN-COUPLED RECEPTOR; FRIZZLED-4; LRP5; MAINTENANCE; DISRUPTION; ACTIVATION; MUTATION; PATHWAY; NORRIN;

D O I：

10.1016/j.devcel.2014.08.018

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Canonical Wnt signaling in endothelial cells (ECs) is required for vascularization of the central nervous system (CNS) and for formation and maintenance of barrier properties unique to CNS vasculature. Gpr124 is an orphan member of the adhesion G protein-coupled receptor family that is expressed in ECs and is essential for CNS angiogenesis and barrier formation via an unknown mechanism. Using canonical Wnt signaling assays in cell culture and genetic loss-and gain-of-function experiments in mice, we show that Gpr124 functions as a coactivator of Wnt7a- and Wnt7b-stimulated canonical Wnt signaling via a Frizzled receptor and Lrp coreceptor and that Gpr124-stimulated signaling functions in concert with Norrin/Frizzled4 signaling to control CNS vascular development. These experiments identify Gpr124 as a ligand-specific coactivator of canonical Wnt signaling.

引用

页码：248 / 256

页数：9

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