GPR37 Membrane Protein Introduction

Introduction of GPR37

GPR37, also known as endothelin B receptor-like protein 1 or parkin-associated endothelin receptor-like receptor, is a protein encoded by the human GPR37 gene. It is a member of the G protein-coupled receptor family which contains seven transmembrane domains and is found in the cell and endoplasmic reticulum membranes. During the past years, studies have reported that GPR37 could interact with Parkin and is involved in juvenile Parkinson disease.

Function of GPR37 Membrane Protein

GPR37 is a member of the G protein-coupled receptor (GPCR) family. Studies have shown that GPR37 is widely expressed in diverse human tissues, which including but not limited to spinal cord, placenta, liver, stomach, and testis. Particular, it is highly expressed in brain regions such as corpus callosum, caudate nucleus, putamen, substantia nigra, hippocampus and cerebellum. As a parkin-associated endothelin-like receptor, GPR37 is reported to be associated with autosomal recessive juvenile Parkinson’s disease. GPR37 could interact with HSPA1A and Parkin (ligase). Moreover, GPR37 is involved in the development of autosomal-recessive juvenile parkinsonism as well as major depressive and bipolar disorders. And the level of GPR37 is significantly increased in patients with AR-JP which indicates that the aggregation of GPR37 is linked to disease pathogenesis. In addition, overexpression of GPR37 in the nigrostriatal region of rats resulted in pathologic changes common to Parkinson’s disease.

Fig.1 GPR37 folding and its role in cell fate. (Smith, 2015)

Application of GPR37 Membrane Protein in Literature

1. Smith B.M., et.al. Mice lacking Gpr37 exhibit decreased expression of the myelin-associated glycoprotein MAG and increased susceptibility to demyelination. Neuroscience. 2017, 358:49-57. PubMed ID: 28642167
   
   

   This article reveals that loss of GPR37 alters oligodendrocyte physiology and increases susceptibility to demyelination, indicating that GPR37 could be a potential drug target for the treatment of demyelinating diseases such as multiple sclerosis.

2. Morató X., et.al. The Parkinson’s disease-associated GPR37 receptor interacts with striatal adenosine A 2A receptor controlling its cell surface expression and function in vivo. Scientific reports. 2017, 7(1):9452. PubMed ID: 28842709
   
   

   This report suggests that GPR37 plays a key role in controlling A2AR biology in the striatum, which may be relevant for PD management.

3. Leinartaité L., Svenningsson P. Folding Underlies Bidirectional Role of GPR37/Pael-R in Parkinson Disease. Trends in pharmacological sciences. 2017, 38(8):749-60. PubMed ID: 28629580
   
   

   This article focuses on the multiple roles of GPR37 with relevance to potential disease modification and symptomatic therapies of Parkinson disease (PD) and highlights unsolved issues in this field.

4. Rial D., et.al. Parkinson’s disease-associated GPR37 receptor regulates cocaine-mediated synaptic depression in corticostriatal synapses. Neuroscience letters. 2017, 638:162-6. PubMed ID: 28007645
   
   

   This article investigates the role of GPR37 in the control of cocaine-mediated electrophysiological effects (synaptic transmission and short-term plasticity) in corticostriatal synapses. It indicates that GPR37 is involved in the cocaine-induced modification of basal synaptic transmission without modifying cocaine effects in short-term plasticity.

5. Wang H., et.al. REG4 promotes peritoneal metastasis of gastric cancer through GPR37. Oncotarget. 2016, 7(19):27874. PubMed ID: 27036049
   
   

   This article reveals that REG4 could promote peritoneal metastasis of gastric cancer through GPR37 and trigger a positive feedback loop.

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Reference

1. Smith, N. J. (2015). Drug discovery opportunities at the endothelin B receptor-related orphan G protein-coupled receptors, GPR37 and GPR37L1. Frontiers in pharmacology, 6, 275.

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