GPR124 Functions as a WNT7-Specific Coactivator of Canonical β-Catenin Signaling
| Autor: | Bofan Wu, Steven Seaman, Enrique Zudaire, Jeffrey S. Rubin, Ming Zhou, Holly Morris, Animesh Shukla, Brad St. Croix, Ekaterina Posokhova, Suresh R. Volate, Mary Beth Hilton, Deborah A. Swing |
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| Rok vydání: | 2015 |
| Předmět: |
Angiogenesis
Transgene Amino Acid Motifs PDZ Domains Mice Transgenic Biology Article General Biochemistry Genetics and Molecular Biology Receptors G-Protein-Coupled Mice Proto-Oncogene Proteins Coactivator Animals Humans Receptor lcsh:QH301-705.5 Wnt Signaling Pathway beta Catenin G protein-coupled receptor Mice Knockout Orphan receptor HEK 293 cells Wnt signaling pathway Brain Endothelial Cells Cell biology Wnt Proteins HEK293 Cells lcsh:Biology (General) Blood-Brain Barrier |
| Zdroj: | Cell Reports, Vol 10, Iss 2, Pp 123-130 (2015) |
| ISSN: | 2211-1247 |
| Popis: | SummaryG protein-coupled receptor 124 (GPR124) is an orphan receptor in the adhesion family of GPCRs, and previous global or endothelial-specific disruption of Gpr124 in mice led to defective CNS angiogenesis and blood-brain barriergenesis. Similar developmental defects were observed following dual deletion of Wnt7a/Wnt7b or deletion of β-catenin in endothelial cells, suggesting a possible relationship between GPR124 and canonical WNT signaling. Here, we show using in vitro reporter assays, mutation analysis, and genetic interaction studies in vivo that GPR124 functions as a WNT7A/WNT7B-specific costimulator of β-catenin signaling in brain endothelium. WNT7-stimulated β-catenin signaling was dependent upon GPR124’s intracellular PDZ binding motif and a set of leucine-rich repeats in its extracellular domain. This study reveals a vital role for GPR124 in potentiation of WNT7-induced canonical β-catenin signaling with important implications for understanding and manipulating CNS-specific angiogenesis and blood-brain barriergenesis. |
| Databáze: | OpenAIRE |
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