Help Privacy Policy Disclaimer
  Advanced SearchBrowse




Journal Article

An integrated model for Gpr124 function in Wnt7a/b signaling among vertebrates


Stainier,  Didier Y. R.
Developmental Genetics, Max Planck Institute for Heart and Lung Research, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available

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(9): 110902. doi:10.1016/j.celrep.2022.110902.

Cite as: https://hdl.handle.net/21.11116/0000-000A-C7D5-5
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.