GPR15 Membrane Protein Introduction

Introduction of GPR15

GPR15 is encoded by the GPR15 gene which is mapped to human chromosome 3q11.2-q13.1 and the mass of GPR15 is 40,787 Da in human. It belongs to the G-protein-coupled receptor (GPCR) family which represents the largest class of cell surface receptors and play an integral role in an enormous array of biological pathways. Besides, GPR15/BOB exhibits the primary structure of a 7-transmembrane domain protein and shares sequence identity with regions of the angiotensin II receptor and GPCRs CXCR2, CXCR4, CCR5, DEZ (chemerin receptor), GPR1 and APJ (apelin receptor).

Function of GPR15 Membrane Protein

The activity of GPR15 is mediated by G proteins, resulting in the activation of adenylyl cyclase and elevating intracellular cAMP. GPR15/BOB is a co-receptor for simian immunodeficiency virus (SIV) and human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2). The majority of HIV-2 envelope glycoproteins and a minority of HIV-1 envelope glycoproteins can use GPR15 as a co-receptor and SIV uses GPR15/BOB to infect cell lines transfected to express the receptor. GPR15/BOB is expressed on several human B and T cell lines including the T/B cell hybrid cell line CEMx174. Besides, GPR15/BOB is expressed by macrophages in synovial tissue and on monocytes and neutrophils in peripheral blood, and expression is up-regulated in RA patients compared to non-RA controls. This orphan receptor, GPR150, on monocytes/macrophages and neutrophils may play a role in RA pathophysiology. What’s more, it has been shown that GPR15 controls homing of regulatory T cells specifically to the large intestine mucosa and thereby regulates local immune homeostasis.

Fig.1 GPR15/Bob-mediated signal transduction (Maresca, 2003).

Application of GPR15 Membrane Protein in Literature

1. Bauer M., et al. Tobacco-smoking induced GPR15-expressing T cells in blood do not indicate pulmonary damage. Bmc Pulmonary Medicine. 2017, 17(1), 159. PubMed ID: 29183299
   
   

   This article reports that the degree of GPR15-expressing cells among T cells as well as the methylation at cg05575921 in granulocytes in blood are both rather signs of tobacco-smoking induced systemic inflammation because they don’t indicate specifically non-cancerous pathological changes in the lungs.

2. Ocón B., et al. A Mucosal and Cutaneous Chemokine Ligand for the Lymphocyte Chemoattractant Receptor GPR15. Frontiers in Immunology. 2017, 8: 1111. PubMed ID: 28936214
   
   

   This article reveals that identification of the chemotactic activity of GPR15L adds to its reported antibacterial and tumor cell growth regulatory functions and suggests the potential of targeting GPR15L-GPR15 interactions for modulation of mucosal and cutaneous inflammation.

3. Kim S.V., et al. GPR15-mediated homing controls immune homeostasis in the large intestine mucosa. Science (New York, NY). 2013, 340(6139), 1456-1459. PubMed ID: 23661644
   
   

   This article describes a T cell-homing receptor for LILP and indicates that GPR15 plays a role in mucosal immune tolerance largely by regulating the influx of regulatory T cells.

4. Blaak H., et al. CCR5, GPR15, and CXCR6 Are Major Coreceptors of Human Immunodeficiency Virus Type 2 Variants Isolated from Individuals with and without Plasma Viremia. Journal of Virology. 2005, 79(3), 1686-1700. PubMed ID: 15650194
   
   

   Authors of this article find that HIV-2 isolates from aviremic individuals commonly use as coreceptors CCR5, GPR15, and CXCR6, as well as an unidentified receptor expressed by U87 cells.

5. Clayton F., et al. Gp120-induced Bob/GPR15 activation: a possible cause of human immunodeficiency virus enteropathy. American Journal of Pathology, 2001, 159(5), 1933-1939. PubMed ID: 11696454
   
   

   This article reports that GPR15 is an inefficient infection-inducing co-receptor, it mediates viral strain-specific gp120-induced calcium signaling at low, physiologically reasonable gp120 concentrations, up to 10,000-fold lower gp120 concentrations than the principal co-receptors. Gp120-induced GPR15 activation is a plausible cause of HIV enteropathy.

GPR15 Preparation Options

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Reference

1. Maresca M, et al. (2003). The virotoxin model of hiv-1 enteropathy: involvement of gpr15/bob and galactosylceramide in the cytopathic effects induced by hiv-1 gp120 in the ht-29-d4 intestinal cell line. Journal of Biomedical Science 10(1), 156-166.

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