P2RY11 Membrane Protein Introduction

Introduction of P2RY11

P2RY11, also known as purinergic receptor P2Y11, purinergic receptor P2Y, is a 40.3 kDa protein and a member of the family of G-protein coupled receptors (GPCRs). It consists of 374 amino acids and is determined to contain 2 exons. In humans, it is encoded by the gene P2RY11 located at the chromosome 19p13.2, where it is adjacent to the SSF1 gene. This intergenic splicing between them is a rare phenomenon in normal mammalian that probably has evolutionary implications. The human P2RY11 shares 33% identical to the human P2RY1 (its closest homolog) and is activated by adenine, however not the uridine nucleotide, to accelerate the pertussis toxin-insensitive phosphoinositide breakdown as well as cyclic AMP formation.

Function of P2RY11 Membrane Protein

Northern blot analysis demonstrated that P2RY11 transcripts are abundantly expressed in the spleen but weakly in the liver and the small intestine. HL60 promyelocytic leukemia cell lines release an endogenous receptor with pharmacological features of the P2RY11 receptor. And data from HL60 and other leukemia-derived cells suggested that the P2RY11 can regulate a cyclic AMP-dependent pathway controlling the granulocyte differentiation. This receptor is coupled to G protein that stimulates both phosphoinositide and adenylyl cyclase pathways and serves as a selective purinoceptor. Naturally existing read-through transcripts, resulting from intergenic splicing of this gene and an upstream gene, PPAN, have been detected. The PPAN-P2RY11 read-through mRNA is ubiquitously found and codes for a fusion protein having an identity with each gene product. In addition, there is an association between P2RY11 and several diseases, such as sleep disorder narcolepsy.

Fig.1 Schematic structure of the human P2Y11 protein. (Degn, 2017)

Application of P2RY11 Membrane Protein in Literature

1. Ohsaki A., et al. A novel mechanism of γ-irradiation-induced IL-6 production mediated by P2Y11 receptor in epidermal keratinocytes. Biol Pharm Bull. 2018, 41(6),925-936. PubMed ID: 29553088
   
   

   In summary, authors suggested that after irradiated, γ-irradiation can induce sustained IL-6 production in HaCaT cells from 33 h, which was mediated by P2Y11 receptor-p38 MAPK-NF-κB pathway and G9a degradation. It was regarded as a new mechanism of cytokine production in γ-irradiation-induced cells.

2. Degn M., et al. Rare missense mutations in P2RY11 in narcolepsy with cataplexy. Brain. 2017, 140(6),1657-1668. PubMed ID: 28460015
   
   

   Six of the eight narcolepsy-related P2Y11 mutations caused significant functional deficits in P2Y11 signaling by both Ca²⁺ and cAMP signaling pathways. Taken together, the data displayed that the reduced P2Y11 signaling played an essential role in developments of narcolepsy with cataplexy.

3. Dreisig K., et al. Validation of antibodies for neuroanatomical localization of the P2Y11 receptor in macaque brain. J Chem Neuroanat. 2016, 78,25-33. PubMed ID: 27515691
   
   

   To advance narcolepsy study it was thus extremely significant to determine the neuroanatomical localization of P2Y11 in the brain with especial emphasis on the hypocretin neurons. This article used western blot (WB), staining of blood smears, and flow cytometry (FC) to find two antibodies for immunohistochemical staining of brain of macaque monkeys.

4. Dreisig K and Kornum B.R. A critical look at the function of the P2Y11 receptor. Purinergic Signal. 2016, 12(3),427-37. PubMed ID: 27246167
   
   

   The article discussed the lack of a murine "P2Y11-like receptor" and highlighted limitations of currently available methods used to explore the P2Y11 receptor. Following these criteria, the evidence suggested a role for P2Y11 receptor in immune activation with cell type-specific effects.

5. Higgins G., et al. Activation of P2RY11 and ATP release by lipoxin A4 restores the airway surface liquid layer and epithelial repair in cystic fibrosis. Am J Respir Cell Mol Biol. 2014, 51(2),178-190. PubMed ID: 24588705
   
   

   This paper provided evidence for a novel role of LXA4 in stimulating apical ATP secretion by Pannexin-1 channels and P2RY11 purinoreceptors activation resulting in an epithelial repair and ASL height increase.

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Reference

1. Degn M, et al. (2017). Rare missense mutations in P2RY11 in narcolepsy with cataplexy. Brain. 140(6), 1657-1668.

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