1. Essential Regulation of CNS angiogenesis by the orphan G protein-coupled receptor GPR124
- Author
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Kuhnert, Frank, Mancuso, Michael R., Shamloo, Amir, Wang, Hsiao-Ting, Choksi, Vir, Florek, Mareike, Su, Hua, Fruttiger, Marcus, Young, William L., Heilshorn, Sarah C., and Kuo, Calvin J.
- Subjects
Membrane proteins -- Properties ,Neovascularization -- Physiological aspects ,Endothelium -- Properties ,G proteins -- Properties ,Science and technology - Abstract
The orphan G protein--coupled receptor (GPCR) GPR124/tumor endothelial marker 5 is highly expressed in central nervous system (CNS) endothelium. Here, we show that complete null or endothelial-specific GPR124 deletion resulted in embryonic lethality from CNS-specific angiogenesis arrest in forebrain and neural tube. Conversely, GPR124 overexpression throughout all adult vascular beds produced CNS-specific hyperproliferative vascular malformations. In vivo, GPR124 functioned cell-autonomously in endothelium to regulate sprouting, migration, and developmental expression of the blood-brain barrier marker Glut1, whereas in vitro, GPR124 mediated Cdc42-dependent directional migration to forebrain-derived, vascular endothelial growth factor--independent cues. Our results demonstrate CNS-specific angiogenesis regulation by an endothelial receptor and illuminate functions of the poorly understood adhesion GPCR subfamily. Further, the functional tropism of GPR124 marks this receptor as a therapeutic target for CNS-related vascular pathologies. 10.1126/science.1196554
- Published
- 2010
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