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

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.

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 Creators:
America, Michelle, Author
Bostaille, Naguissa, Author
Eubelen, Marie, Author
Martin, Maud, Author
Stainier, Didier Y. R.1, Author           
Vanhollebeke, Benoit, Author
Affiliations:
1Developmental Genetics, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591697              

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 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.

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 Dates: 2022-05-31
 Publication Status: Published online
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Title: CELL REPORTS
Source Genre: Journal
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Pages: - Volume / Issue: 39 (9) Sequence Number: 110902 Start / End Page: - Identifier: ISSN: 2211-1247