Biology:GPR156
GPR156 (G protein-coupled receptor 156), is a human gene which encodes a G protein-coupled receptor belonging to metabotropic glutamate receptor subfamily.[1] By sequence homology, this gene was proposed as being a possible GABAB receptor subunit; however, when expressed in cells alone or with other GABAB subunits, no response to GABAB ligands could be detected. In vitro studies on GPR156 constitutive activity revealed a high level of basal activation and coupling with members of the Gi/Go heterotrimeric G protein family.[2] In 2021, an article was reported that GPR156 modulates hair cell orientation in the cochlea.[3] Also, it was proposed that GPR156 is related to congenital hearing loss.[4] GPR156 in complex with any of the Gi/o heterotrimers regulates the hair cell orientation.[5] In 2024, molecular structures of G-free and Go-bound GPR156 were characterized by using cryogenic electron microscopy.[6]
Structure
Among class C GPCR family members, GPR156 is unique because it lacks a large extracellular domain. Structural analyses revealed that the asymmetric binding of Go-protein to GPR156 triggers conformational change of its cytoplasmic face without altering dimer interface.[6] Although the inactive class C GPCRs undergo rearrangement of their dimeric interface, the agonist- and/or the positive allosteric modulator-bound class C GPCRs retain their dimeric interface upon G-protein binding. Thus, the G-free GPR156 is likely to represent an active state.[6] Structural and functional analyses suggest that abundant endogenous phospholipids, receptor dimerization, and the G-protein binding-induced conformational change of the cytoplasmic face are the primary reasons for constitutive activation of GPR156.[6] Phosphatidylglycerol further stimulates the activity of GPR156, which suggests the environmental changes of the phospholipid composition may regulate the GPR156 activity.[6]
References
- ↑ "Entrez Gene: GPR156 G protein-coupled receptor 156". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=165829.
- ↑ "In vitro profiling of orphan G protein coupled receptor (GPCR) constitutive activity". British Journal of Pharmacology 178 (15): 2963–2975. August 2021. doi:10.1111/bph.15468. PMID 33784795.
- ↑ "EMX2-GPR156-Gαi reverses hair cell orientation in mechanosensory epithelia". Nature Communications 12 (1): 2861. May 2021. doi:10.1038/s41467-021-22997-1. PMID 34001891. Bibcode: 2021NatCo..12.2861K.
- ↑ "Novel GPR156 variants confirm its role in moderate sensorineural hearing loss". Scientific Reports 13 (1): 17010. October 2023. doi:10.1038/s41598-023-44259-4. PMID 37814107. Bibcode: 2023NatSR..1317010R.
- ↑ "Inhibitory G proteins play multiple roles to polarize sensory hair cell morphogenesis". eLife 12. April 2024. doi:10.7554/eLife.88186.1. PMID 38651641.
- ↑ 6.0 6.1 6.2 6.3 6.4 "Constitutive activation mechanism of a class C GPCR". Nature Structural & Molecular Biology 31 (4): 678–687. April 2024. doi:10.1038/s41594-024-01224-7. PMID 38332368.
Further reading
- "Molecular cloning and characterisation of a novel GABAB-related G-protein coupled receptor". Brain Research. Molecular Brain Research 110 (2): 305–317. February 2003. doi:10.1016/S0169-328X(02)00662-9. PMID 12591167.
- "The G protein-coupled receptor repertoires of human and mouse". Proceedings of the National Academy of Sciences of the United States of America 100 (8): 4903–4908. April 2003. doi:10.1073/pnas.0230374100. PMID 12679517. Bibcode: 2003PNAS..100.4903V.
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