PUBLICATION
An integrated model for Gpr124 function in Wnt7a/b signaling among vertebrates
- Authors
- America, M., Bostaille, N., Eubelen, M., Martin, M., Stainier, D.Y.R., Vanhollebeke, B.
- ID
- ZDB-PUB-220602-17
- Date
- 2022
- Source
- Cell Reports 39: 110902 (Journal)
- Registered Authors
- Stainier, Didier, Vanhollebeke, Benoit
- Keywords
- BBB, CP: Cell biology, Dlg4, Gpr124, Magi3, Reck, Wnt/β-catenin signaling, Wnt7a, Wnt7b, blood-brain barrier, brain angiogenesis
- MeSH Terms
-
- Animals
- Central Nervous System
- Humans
- Ligands
- Mice
- Receptors, G-Protein-Coupled*/metabolism
- Wnt Signaling Pathway*
- Zebrafish
- PubMed
- 35649360 Full text @ Cell Rep.
Citation
America, M., Bostaille, N., Eubelen, M., Martin, M., Stainier, D.Y.R., Vanhollebeke, B. (2022) An integrated model for Gpr124 function in Wnt7a/b signaling among vertebrates. Cell Reports. 39:110902.
Abstract
Within the central nervous system, Wnt7a/b are unambiguously discriminated from other Wnt ligands by an endothelial receptor complex made of the glycosylphosphatidylinositol (GPI)-anchored Reck and the adhesion G protein-coupled receptor (GPCR) Gpr124. Reck is a Wnt7a/b-specific receptor, while Gpr124 facilitates the delivery of Reck-bound Wnt7a/b ligands to Frizzled, through partially characterized mechanisms. We report that, in zebrafish, the Gpr124-Frizzled interactions are dominated by intracellular scaffolds that exploit the striking molecular mimicry between Gpr124 and Frizzled intracellular domains (ICDs): an internal Dvl-binding motif and a C-terminal ETTV motif that recruits Dlg4 and Magi3. By contrast, mammalian Gpr124 receptors exhibit an ICD-independent interaction mechanism governed by species-specific attributes of their transmembrane and extracellular domains. This mechanism seemingly evolved to replace the Dvl-mediated mechanism. By contrasting zebrafish, mouse, and human Gpr124, this study provides insights into the evolution of Gpr124/Reck function across the vertebrate clade, a receptor complex uniquely implicated in Wnt ligand-specific cellular responses.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping