PUBLICATION

The adhesion GPCR Adgrg6 (Gpr126): Insights from the zebrafish model

Authors
Baxendale, S., Asad, A., Shahidan, N.O., Wiggin, G.R., Whitfield, T.T.
ID
ZDB-PUB-210319-21
Date
2021
Source
Genesis (New York, N.Y. : 2000)   59(4): e23417 (Review)
Registered Authors
Asad, Anzar, Baxendale, Sarah, Whitfield, Tanya T.
Keywords
Adgrg6, Gpr126, aGPCR, drug screening, heart, inner ear, myelination, skeleton, zebrafish
MeSH Terms
  • Animals
  • Arthrogryposis/genetics*
  • Arthrogryposis/metabolism
  • Disease Models, Animal
  • Receptors, G-Protein-Coupled/genetics
  • Receptors, G-Protein-Coupled/metabolism*
  • Signal Transduction
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
33735533 Full text @ Genesis
Abstract
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes