Publikationsdatum:
2010-11-13
Beschreibung:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3099479/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3099479/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuhnert, Frank -- Mancuso, Michael R -- Shamloo, Amir -- Wang, Hsiao-Ting -- Choksi, Vir -- Florek, Mareike -- Su, Hua -- Fruttiger, Marcus -- Young, William L -- Heilshorn, Sarah C -- Kuo, Calvin J -- 1DP2 OD006477/OD/NIH HHS/ -- 1R01HL074267/HL/NHLBI NIH HHS/ -- 1R01NS052830/NS/NINDS NIH HHS/ -- 1R01NS064517/NS/NINDS NIH HHS/ -- 1R21 NS058600/NS/NINDS NIH HHS/ -- G0501711/Medical Research Council/United Kingdom -- GM07365/GM/NIGMS NIH HHS/ -- P01NS44155/NS/NINDS NIH HHS/ -- R01 CA095654/CA/NCI NIH HHS/ -- R01 CA095654-01/CA/NCI NIH HHS/ -- R01 HL074267/HL/NHLBI NIH HHS/ -- R01 HL074267-02/HL/NHLBI NIH HHS/ -- R01 NS052830/NS/NINDS NIH HHS/ -- R01 NS052830-01/NS/NINDS NIH HHS/ -- R01 NS064517/NS/NINDS NIH HHS/ -- R01 NS064517-02/NS/NINDS NIH HHS/ -- R01NS27713/NS/NINDS NIH HHS/ -- R21 NS070153/NS/NINDS NIH HHS/ -- T32 CA009302/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2010 Nov 12;330(6006):985-9. doi: 10.1126/science.1196554.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Hematology Division, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21071672" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Animals
;
Blood Vessels/abnormalities
;
Blood-Brain Barrier/metabolism
;
Cell Movement
;
Embryonic Development
;
Endothelial Cells/physiology
;
Endothelium, Vascular/embryology/metabolism
;
Gene Deletion
;
Glucose Transporter Type 1/metabolism
;
Mesencephalon/blood supply/embryology/metabolism
;
Mice
;
Mice, Knockout
;
Mice, Transgenic
;
*Neovascularization, Physiologic
;
Neural Tube/*blood supply/embryology/metabolism
;
Prosencephalon/*blood supply/embryology/metabolism
;
Receptors, G-Protein-Coupled/genetics/*metabolism
;
Rhombencephalon/blood supply/embryology/metabolism
;
Telencephalon/blood supply/embryology/metabolism
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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