PUBLICATION
The orphan G protein-coupled receptor 25 (GPR25) is activated by Apelin and Apela in non-mammalian vertebrates
- Authors
- Zhang, J., Wan, Y., Fang, C., Chen, J., Ouyang, W., Li, J., Wang, Y.
- ID
- ZDB-PUB-180508-9
- Date
- 2018
- Source
- Biochemical and Biophysical Research Communications 501(2): 408-414 (Journal)
- Registered Authors
- Keywords
- Apela, Apelin, GPR25, Pigeons, Spotted gars, Zebrafish
- MeSH Terms
-
- Animals
- Chemokines/genetics
- Chemokines/metabolism*
- Cloning, Molecular
- Columbidae/genetics
- Cyclic AMP/metabolism
- Fish Proteins/genetics
- HEK293 Cells
- Humans
- Receptors, G-Protein-Coupled/genetics*
- Receptors, G-Protein-Coupled/metabolism
- Vertebrates/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 29727602 Full text @ Biochem. Biophys. Res. Commun.
Citation
Zhang, J., Wan, Y., Fang, C., Chen, J., Ouyang, W., Li, J., Wang, Y. (2018) The orphan G protein-coupled receptor 25 (GPR25) is activated by Apelin and Apela in non-mammalian vertebrates. Biochemical and Biophysical Research Communications. 501(2):408-414.
Abstract
G protein-coupled receptor 25 (GPR25) is an orphan G protein-coupled receptor in vertebrates, that has been implicated to be associated with autoimmune diseases and regulate blood pressure in humans. However, the endogenous ligand of GPR25 remains unknown in vertebrates. Here, we reported that in non-mammalian vertebrates (zebrafish, spotted gars, and pigeons), GPR25 could be activated by Apelin and Apela peptides, which are also the two endogenous ligands of vertebrate Apelin receptor (APLNR). Using the pGL3-CRE-luciferase reporter assay and confocal microscopy, we first demonstrated that like APLNR, zebrafish GPR25 expressing in HEK293 cells could be effectively activated by zebrafish Apelin and Apela peptides, leading to the inhibition of forskolin-stimulated cAMP production and receptor internalization. Like zebrafish GPR25, pigeon and spotted gar GPR25 could also be activated by Apelin and Apela, and their activation could inhibit forskolin-induced cAMP accumulation. Interestingly, unlike zebrafish (/spotted gar/pigeon) GPR25, human GPR25 could not be activated by Apelin and Apela under the same experimental conditions. RNA-seq analysis further revealed that GPR25 is expressed in a variety of tissues, including the testes and intestine of zebrafish/spotted gars/humans, implying the potential roles of GPR25 signaling in many physiological processes in vertebrates. Taken together, our data not only provides the first proof that the orphan receptor GPR25 possesses two potential ligands 'Apelin and Apela' and its activation decreases intracellular cAMP levels in non-mammalian vertebrates, but also facilitates to unravel the physiological roles of GPR25 signaling in vertebrates.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping