| First Author | Posokhova E | Year | 2015 |
| Journal | Cell Rep | Volume | 10 |
| Issue | 2 | Pages | 123-30 |
| PubMed ID | 25558062 | Mgi Jnum | J:222817 |
| Mgi Id | MGI:5645632 | Doi | 10.1016/j.celrep.2014.12.020 |
| Citation | Posokhova E, et al. (2015) GPR124 functions as a WNT7-specific coactivator of canonical beta-catenin signaling. Cell Rep 10(2):123-30 |
| abstractText | G 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 beta-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 beta-catenin signaling in brain endothelium. WNT7-stimulated beta-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 beta-catenin signaling with important implications for understanding and manipulating CNS-specific angiogenesis and blood-brain barrier-genesis. |
