GPR85 Membrane Protein Introduction

Introduction of GPR85

Probable G-protein coupled receptor 85 (GPR85, SREB2) is a protein that in humans is encoded by the GPR85 gene. Among the related pathways of GPR85 are Peptide ligand-binding receptors. Gene Ontology (GO) annotations related to this gene include G-protein coupled receptor activity. An important paralog of this gene is GPR173. The SREB (Super Conserved Receptor Expressed in Brain) family - SREB1 (GPR27), SREB2 (GPR85), and SREB3 (GPR173) - is a particular subfamily of the GPCRs. They share 52-63% amino-acid identity and have lower homology to other GPCR subfamilies. The unique characteristic of the SREB family is the high conservation of the amino-acid sequence across species. SREB2, located on Chromosome 7q31, is an orphan GPCR of 7.5 kB that generates nine transcripts encoding for four proteins through alternative splicing.

Function of GPR85 Membrane Protein

G protein-coupled receptors (GPCRs) are the largest family of membrane surface receptors, essential for signal transduction in central nervous system, and a preferred therapeutic target for psychiatric and neurological disorders. More recently, a possible role of GPR85 in autism and possibly attention deficit hyperactivity disorder, Tourette’s syndrome and intellectual disability has emerged. Thus, it is conceivable that genetic variation in GPR85 might contribute to a spectrum of neurodevelopmental psychiatric disorders, analogous to other genetic risk factors associated with risk for schizophrenia. Two single-nucleotide polymorphisms (SNPs) in GPR85 are nominally associated with schizophrenia risk.

Fig.1 SREB2-genotype effects on BOLD response during the PICT task. (Radulescu, 2013)

Application of GPR85 Membrane Protein in Literature

1. Radulescu E., et al. Effect of schizophrenia risk-associated alleles in SREB2 (GPR85) on functional MRI phenotypes in healthy volunteers. Neuropsychopharmacology. 2013, 38(2): 341-9. PubMed ID: 22968816
   
   

   The article reveals that genetic variants in GPR85 have been associated with risk for schizophrenia. Trends in the same direction were present for GPR85 in the right occipital cortex and right fusiform gyrus.

2. Chen Q., et al. SREB2/GPR85, a schizophrenia risk factor, negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent learning and memory. Eur J Neurosci. 2012, 36(5): 2597-608. PubMed ID: 22697179
   
   

   The article indicates that SREB2 is a negative regulator of adult neurogenesis and consequential cognitive functions. Inhibition of SREB2 function may be a novel approach to enhance hippocampal adult neurogenesis and cognitive abilities to ameliorate core symptoms of psychiatric patients.

3. Matsumoto M., et al. The evolutionarily conserved G protein-coupled receptor SREB2/GPR85 influences brain size, behavior, and vulnerability to schizophrenia. Proc Natl Acad Sci U S A. 2008, 105(16): 6133-8. PubMed ID: 18413613
   
   

   Authors in this group found that GPR85 influences brain size. GPR85 may be a potential risk factor for psychiatric disorders and its pathway can be used as a target for psychiatric therapy.

4. Matsumoto M., et al. A conserved mRNA expression profile of SREB2 (GPR85) in adult human, monkey, and rat forebrain. Brain Res Mol Brain Res. 2005, 138(1): 58-69. PubMed ID: 15893849
   
   

   This article focuses on the possible link between SREB family and neural plasticity. SREB2 mRNA was expressed in neurons throughout the brain and the most abundant expression was detected in the hippocampal dentate gyrus in all species examined.

5. Fujita-Jimbo E., et al. The association of GPR85 with PSD-95-neuroligin complex and autism spectrum disorder: a molecular analysis. Mol Autism. 2015, 6: 17. PubMed ID: 25780553
   
   

   This article reports that GPR85 is associated with postsynaptic density protein (PSD)-95 linked with NLGN in the brain. GPR85 carrying the mutations detected in ASD patients disturbs dendrite formation.

GPR85 Preparation Options

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Reference

1. Radulescu E, et al. (2013). Effect of schizophrenia risk-associated alleles in SREB2 (GPR85) on functional MRI phenotypes in healthy volunteers. Neuropsychopharmacology. 38(2): 341-9.

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