The adhesion GPCR Adgrg6 (Gpr126): Insights from the zebrafish model
| Autor: | Giselle R. Wiggin, Tanya T. Whitfield, Sarah Baxendale, Nahal O Shahidan, Anzar Asad |
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| Rok vydání: | 2021 |
| Předmět: |
Mutant
Biology Receptors G-Protein-Coupled 03 medical and health sciences 0302 clinical medicine Endocrinology Genetics Animals Zebrafish Inner ear morphogenesis 030304 developmental biology G protein-coupled receptor Arthrogryposis 0303 health sciences Drug discovery Cell Biology Zebrafish Proteins biology.organism_classification CUB domain Phenotype Cell biology Disease Models Animal Signal transduction 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Genesis (New York, N.Y. : 2000)REFERENCES. 59(4) |
| ISSN: | 1526-968X |
| Popis: | Adhesion GPCRs are important regulators of conserved developmental processes and represent an untapped pool of potential targets for drug discovery. The adhesion GPCR Adgrg6 (Gpr126) has critical developmental roles in Schwann cell maturation and inner ear morphogenesis in the zebrafish embryo. Mutations in the human ADGRG6 gene can result in severe deficits in peripheral myelination, and variants have been associated with many other disease conditions. Here, we review work on the zebrafish Adgrg6 signaling pathway and its potential as a disease model. Recent advances have been made in the analysis of the structure of the Adgrg6 receptor, demonstrating alternative structural conformations and the presence of a conserved calcium-binding site within the CUB domain of the extracellular region that is critical for receptor function. Homozygous zebrafish adgrg6 hypomorphic mutants have been used successfully as a whole-animal screening platform, identifying candidate molecules that can influence signaling activity and rescue mutant phenotypes. These compounds offer promise for further development as small molecule modulators of Adgrg6 pathway activity. |
| Databáze: | OpenAIRE |
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