GPR3 Membrane Protein Introduction

Introduction of GPR3

GPR3 is encoded by the GPR3 gene. It belongs to the G-protein-coupled receptor (GPCR) family which is one of the largest and most studied families of proteins because its members are involved in an extraordinary number of physiological functions. It is cloned and sequenced in the mid-1990s along with GPR6 originally. Even though sphingosine-1-phosphate (S-1-P) and G_s protein can active and couple to GPR3 constitutively, the natural ligand of GPR3 is still controversial. It is still one of orphan G protein-coupled receptors.

Function of GPR3 Membrane Protein

GPR3 expresses in the central nervous system mainly, suggesting that GPR3 may be involved in regulating the health and disease of the brain. GPR3 is implicated in the early phases of cocaine reinforcement, resulting in altering emotional behaviors. Meanwhile, GPR3 has been reported to participate in the development of neuropathic pain, so that GPR3 can regulate morphine-induced antinociception. As to the expression pattern of GRP3 in the central nervous system, GPR3 may play roles in Alzheimer’s disease. According to the hypothesis, GPR3 promotes the production of amyloid-β, which is the main component of amyloid plaques in Alzheimer patients’ brains and are important in Alzheimer's disease. Regarding the possible endogenous ligands of GPR3, some studies report that the sphingosine-1-phosphate (S-1-P) and G_s protein are agonists for both GPR3 and GPR6 because S-1-P and G_s protein can induce cAMP production and Ca²⁺ mobilization in the GPR3 or GPR6 expressing cells. However, the conclusion of S-1-P or G_s protein as endogenous ligands for GPR3 and GRP6 is challenged by other research groups because they cannot repeat the same experimental results. GPR3 is still considered orphan GPCRs without specific ligand because of the controversy.

Fig.1 Structure of GPR3 membrane protein. (Zhou, 2017)

Application of GPR3 Membrane Protein in Literature

1. Laun A.S., et al. GPR3 and GPR6, novel molecular targets for cannabidiol. Biochem. Biophys. Res. Commun. 2017, 490(1):17-21. PubMed ID: 28571738
   
   

   This article demonstrates that cannabidiol can act as a novel agonist for both GPR3 and GPR6, suggesting the potential therapeutic effects of cannabidiol in Alzheimer's disease and Parkinson's disease.

2. Kovanci E., et al. Oocyte-specific G-protein-coupled receptor 3 (GPR3): no perturbations found in 82 women with premature ovarian failure (first report). Fertility and Sterility. 2008, 90(4):1269-1271. PubMed ID: 17953967
   
   

   Authors in this group apply to denaturing high-performance liquid chromatography and DNA sequencing to detect the GPR3 sequence variants in 82 predominantly North American Caucasian women with premature ovarian failure (POF), suggesting that the mutations of GPR3 are not a common explanation for POF in this population.

3. Firmani L.D., et al. The switch from cAMP-independent to cAMP-dependent arrest of meiotic prophase is associated with coordinated GPR3 and CDK1 expression in mouse oocytes. Dev. Biol. 2018, 434(1):196-205. PubMed ID: 29274320
   
   

   This article reveals that oocytes from GPR3 double knock out mice have significantly lower CDK1 levels than WT mice at the same stage of follicle development, suggesting GPR3 may be involved in regulation meiotic by regulating CDK1 levels.

4. Jensen T., et al. The identification of GPR3 inverse agonist AF64394; The first small molecule inhibitor of GPR3 receptor function. Bioorganic & Medicinal Chemistry Letters. 2014, 24(22):5195-5198. PubMed ID: 25442311
   
   

   Authors in this group report firstly a novel GPR3 inverse agonist AF64394, which can inhibit the biological function of GPR3 and it’s structure-activity relationships.

5. Li H., et al. Pentoxifylline inhibits pulmonary inflammation induced by infrarenal aorticcross-clamping dependent of adenosine receptor A2A. Am J Transl Res. 2016, 8(5), 2210-21. PubMed ID: 27347328
   
   

   This article demonstrates that GPR3 regulates the amyloidogenic proteolysis of amyloid precursor protein in Alzheimer's disease mice model, suggesting that GPR3 may be a novel drug target for Alzheimer's disease treatment.

GPR3 Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-GPR3 antibody development services.

• Magic™ Membrane Protein Production Platform
• Magic™ Anti-Membrane Protein Antibody Discovery Platform

As a forward-looking research institute as well as a leading customer service provider in the field of membrane protein, Creative Biolabs is famous for successfully accomplishing numerous challenging projects including generation of many functional membrane proteins among our worldwide customers. Please feel free to contact us for more detailed information.

Reference

1. Zhou X. E., et al. (2017) Identification of Phosphorylation Codes for Arrestin Recruitment by G Protein-Coupled Receptors. Cell. 170(3):457-469.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.