P2RY10 Membrane Protein Introduction

Introduction of P2RY10

P2RY10, also known as P2Y receptor family member 10, purinergic receptor P2Y, purinergic receptor P2Y10, P2Y-Like receptor, G-protein coupled purinergic receptor P2Y10, or LYPSR2, is a G-protein coupled receptor (GPCR) protein and has a molecular weight of 38.8 kDa. In humans, it is encoded by the gene P2RY10 which resides on the chromosome Xq21.1. And there exists a pseudogene for P2RY10 nearby on the chromosome X. This receptor is a member of the purine and pyrimidine nucleotide receptor family that is coupled to G proteins. Multiple alternatively spliced transcripts of P2RY10 gene have been observed. P2RY10 associated pathways are signaling by GPCR and peptide ligand-binding receptors.

Function of P2RY10 Membrane Protein

P2RY10 also belongs to the family of GPCR, preferentially activated by adenosine as well as uridine nucleotides. It acts as a receptor for lysophosphatidic acid and sphingosine-1-phosphate. P2RY10 activation leads to the mobilization of inositol 1,4,5-trisphosphate-sensitive Ca²⁺ storages, activation of inward plasma membrane currents, as well as stimulation of diacylglyceride-dependent protein kinases. It is demonstrated that this receptor is weakly present in blood leukocytes but nearly undetectable in undifferentiated cells and the following granulocytic differentiation. And P2RY10 can be upregulated during the promyelocytic cell differentiation along monocytic pathways. Additionally, P2RY10 is one of the highly upregulated genes at the late differentiation phage during in vitro eosinophilopoiesis. Furthermore, P2RY10, together with GPR34 and GPR174, is activated by lysophosphatidylserine (LysoPS), an endogenous lipid mediator. These three receptors are LysoPS-specific human GPCRs and constitute a LysoPS receptor family.

Fig.1 (A) Phylogenetic tree of the amino acid sequences of human P2Y family members. (Makide, 2014) (B) Expression of LysoPS receptors P2Y10 for LysoPS in PB leukocytes. (Hwang, 2018)

Application of P2RY10 Membrane Protein in Literature

1. Hwang S.M., et al. Lysophosphatidylserine receptor P2Y10: A G protein-coupled receptor that mediates eosinophil degranulation. Clin Exp Allergy. 2018. PubMed ID: 29700886
   
   

   The article discussed the human P2Y10 expression and function in cord blood (CB)-derived and peripheral blood (PB) eosinophils. LysoPS promoted eosinophil degranulation by P2Y10 and thus, P2Y10 was an attractive therapeutic target to control eosinophil-related diseases.

2. Shinjo Y., et al. Lysophosphatidylserine suppresses IL-2 production in CD4 T cells through LPS₃/GPR174. Biochem Biophys Res Commun. 2017, 494(1-2),332-338. PubMed ID: 29017923
   
   

   Recent report showed that three G protein-coupled receptors, LPS1/GPR34, LPS2/P2Y10, and LPS3/GPR174, are detected to react specifically with LysoPS, which raised the possibility that LysoPS exerting its roles by these receptors. Conclusively, LPS3 was expressed in many T cell subtypes and participated in the suppression of interleukin-2 production in CD4 T cells.

3. Jung S., et al. Conformational constraint of the glycerol moiety of lysophosphatidylserine affords compounds with receptor subtype selectivity. J Med Chem. 2016, 59(8),3750-3776. PubMed ID: 27077565
   
   

   To elevate potency and receptor selectivity, LysoPS analogs with the conformational constraints of the glycerol moiety had been designed and synthesized. The reduced structural flexibility by fixation of the glycerol framework of LysoPS, and associated structures identified the compounds exhibiting high potency and selectivity for the activation of P2Y10 or GPR34.

4. Ikubo M., et al. Structure-activity relationships of lysophosphatidylserine analogs as agonists of G-protein-coupled receptors GPR34, P2Y10, and GPR174. J Med Chem. 2015, 58(10),4204-4219. PubMed ID: 25970039
   
   

   There were two LysoPS-specific human G-protein-coupled receptors (GPCRs), P2Y10 (LPS2) and GPR174 (LPS3), recently had been identified by the ligand screening of orphan GPCRs. Herein, authors examined the structure-activity relationships of several synthetic LysoPS analogs toward above deorphanized LysoPS receptors.

5. Makide K., et al. Novel lysophosphoplipid receptors: their structure and function. J Lipid Res. 2014, 55(10),1986-1995. PubMed ID: 24891334
   
   

   This report currently found a GPCR for LPI (GPR55) and discovered three GPCRs for LysoPS including GPR34/LPS1, P2Y10/LPS2, and GPR174/LPS3. This review focused on these newly identified GPCRs and summarized actions of LPI and LysoPS as lipid mediators.

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References

1. Makide K, et al. (2014). Novel lysophosphoplipid receptors: their structure and function. J Lipid Res. 55(10), 1986-1995.
2. Hwang SM, et al. (2018). Lysophosphatidylserine receptor P2Y10: A G protein-coupled receptor that mediates eosinophil degranulation. Clin Exp Allergy.

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