GPR173 Membrane Protein Introduction

Introduction of GPR173

GPR173, also designated SREB3, belongs to the SREB subfamily of G protein-coupled receptors, which are highly conserved among vertebrate species and notably expressed in the brain and ovary. This family, designated super conserved receptor expressed in Brain, is comprised of at least three members, termed SREB1, SREB2, and SREB3. GPR173 is encoded by the GPR173 gene, which located at Xp11. The GPR173 amino acid sequence is also highly conserved between rat and human, at 99% identical.

Function of GPR173 Membrane Protein

GPR173 is highly expressed in areas related to reproductive control including the MPO, AVPV, Arc, VMH, and MeA. These areas have a dense expression of estrogen receptor-α, and both the hypothalamic and the adenohypophysis actions of phoenixin require the participation of GPR173, which is endogenously expressed in those tissues. Beyond that, GPR173 is identified as a novel X chromosome susceptibility gene for systemic lupus erythematosus (SLE) by Meta-analysis of GWAS on both Chinese and European populations. More concretely, rs13440883 in GPR173 is identified as a novel X-linked locus associated with SLE. These findings improve the understanding of the role of the X chromosome in this prototypical autoimmune disease that predominantly affects women. What’ s more, GPR173 is strongly expressed in both GnRH and kisspeptin cell models and small interfering RNA knockdown of GPR173 prevented the PNX-mediated up-regulation of GnRH, GnRH-R, and Kiss1 mRNA expression and the down-regulation of C/EBP-β mRNA expression.

Fig.1 Putative Model of Mouse GPR173 Disposition in the Membrane. (Larco, 2013)

Application of GPR173 Membrane Protein in Literature

1. Zhang H, et al. Meta-analysis of GWAS on both Chinese and European populations identifies GPR173 as a novel X chromosome susceptibility gene for SLE. Arthritis Research & Therapy. 2018, 20(1), 92. PubMed ID: 29724251
   
   

   This article reports that Single-nucleotide polymorphism rs13440883 in GPR173 was found to be significantly associated with systemic lupus erythematosus (SLE). Authors identify GPR173 as a novel X chromosome susceptibility gene for SLE. This finding emphasizes the importance of the X chromosome in disease pathogenesis and highlights the role of sex chromosomes in the female bias of SL.

2. Treen A.K., et al. Phoenixin activates immortalized GnRH and kisspeptin neurons through the novel receptor GPR173. Molecular Endocrinology. 2016, 30(8), me. 2016-1039. PubMed ID: 27268078
   
   

   This article reveals that PNX acts through GPR173 to activate the cAMP/protein kinase A pathway through CREB, and potentially C/EBP-β and/or Oct-1 to increase GnRH, GnRH-R, and Kiss1 gene expression, ultimately having a stimulatory effect on reproductive function.

3. Stein L.M., et al. Hypothalamic Action of Phoenixin to Control Reproductive Hormone Secretion in Females: Importance of the Orphan G Protein-Coupled Receptor GPR173. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2016, 311(3), R489. PubMed ID: 27440717
   
   

   This study is the first to demonstrate a functional relationship between PNX and GPR173 in reproductive physiology and identify a potential therapeutic target for ovulatory dysfunction. In cultured pituitary cells, siRNA-targeted compromise of GPR173 abrogated PNX's action to potentiate GnRH-stimulated LH secretion. In addition, knockdown of endogenous GPR173, which localized to several hypothalamic sites related to reproductive function, not only significantly extended the estrous cycle but also prevented the PNX-induced LH secretion in diestrous, female rats.

4. Larco D.O., et al. The Novel Actions of the Metabolite GnRH-(1-5) are Mediated by a G Protein-Coupled Receptor. Frontiers in Endocrinology. 2013, 4, 83. PubMed ID: 23847594
   
   

   Authors in this article demonstrate the novel actions of the Metabolite GnRH-(1-5) are mediated by the activation of a G protein-coupled receptor. their findings suggest that GnRH-(1-5) may play a developmental function in addition to regulating developing cells.

GPR173 Preparation Options

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Reference

1. Larco D O, et al. (2013). The Novel Actions of the Metabolite GnRH-(1-5) are Mediated by a G Protein-Coupled Receptor. Frontiers in Endocrinology. 4, 83.

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