P2RY13 Membrane Protein Introduction

Introduction of P2RY13

P2RY13, also known as purinergic receptor P2Y13, purinergic receptor P2Y, GPR86, GPR94, FKSG77, GPCR1, or SP174, is an approximately 41 kDa G protein-coupled receptor (GPCR) which is composed of 354 amino acids. GPCR plays a role in cell communication and is characterized by an intracellular C terminus, seven transmembrane regions, and an extracellular N terminus. P2RY13 is a receptor for ADP and in humans, encoded by the P2RY13 gene mapping at the chromosome 3q25.1. It is known to be activated by ADP and probably plays a role in the hematopoiesis and immune system. This receptor is strongly expressed in the spleen and adult brain, while at lower levels in placenta, liver, lung, thymus, uterus, stomach, testis, spinal cord, small intestine, fetal brain, and adrenal gland.

Function of P2RY13 Membrane Protein

At present, there are eight nucleotide P2Y receptors are known in mammalian, including P2RY1, P2RY2, P2RY4, P2RY6, P2RY11-14. The distribution of P2Y receptors in diverse tissues indicates that they accomplish key roles in certain physiological and pathological situations. P2RY13 as one of the latest P2Y receptors identified recently is a new member of the Gi-coupled P2Y receptor subfamily that can respond to ADP, along with P2RY12 and P2RY14. Pharmacology analysis draws attention to this novel ADP receptor, which has a pharmacological overlap with P2RY12 receptors and is equipped with unique features and functions. The P2RY12, 13, 14 genes all reside on the human chromosome 3q25.1 and their high-level sequence homology supports their evolutionary origin by gene duplication. P2RY13 is versatile in its signaling, extending beyond the normal signaling of a Gi-coupled receptor. It not only can couple to various G proteins but also can trigger a number of intracellular pathways correlated with the activation of mitogen-activated protein kinases (MAPKs) and the phosphatidylinositol 3-kinase axis.

Fig.1 Schematic representation of the intracellular cascades triggered by 2MeSADP (activating both P2Y1 and P2Y13 receptors) stimulation in rat cerebellar astrocytes. (Pérez-Sen, 2015)

Application of P2RY13 Membrane Protein in Literature

1. Stefani J., et al. Disruption of the microglial ADP receptor P2Y13 enhances adult hippocampal neurogenesis. Front Cell Neurosci. 2018, 12,134. PubMed ID: 29867367
   
   

   The result suggested that P2Y13 receptor-activated microglia constitutively moderated hippocampal neurogenesis. Here, selective P2Y13R antagonists were able to promote neurogenesis in pathological conditions related to impaired hippocampal neurogenesis.

2. Zhou R., et al. Activation of spinal dorsal horn P2Y13 receptors can promote the expression of IL-1β and IL-6 in rats with diabetic neuropathic pain. J Pain Res. 2018, 11,615-628. PubMed ID: 29628771
   
   

   Intrathecal MRS2211 generated an anti-nociceptive effect during early-stage diabetic neuropathic pain (DNP). A possible mechanism implicated in MRS2211-induced analgesia was that blocking P2Y13 receptor can down-regulate expressions of IL-1β and IL-6, which later inhibited the activation of JAK2/STAT3 signaling pathway.

3. Quintas C., et al. Microglia P2Y13 receptors prevent astrocyte proliferation mediated by P2Y1 receptors. J Front Pharmacol. 2018, 9,418. PubMed ID: 29773988
   
   

   In summary, this paper showed that microglia control P2Y1 and P2Y12 receptor-mediated astroglial proliferation via a P2Y12 and P2Y13 receptor-mediated mechanism alternative to the IL-1β suppressive pathway that might implicate the contribution of the cytokines IL-1α and TNF-α.

4. Pérez-Sen R., et al. An update on P2Y13 receptor signalling and function. Adv Exp Med Biol. 2017, 1051,139-168. PubMed ID: 28815513
   
   

   This article summarized their current understanding of the elusive receptor, not only at the molecular and pharmacological level but also in its signaling properties and specific functions, beneficial to clarify the role of P2Y13 receptors in pathological circumstances.

5. Jacques F.J., et al. Nucleotide P2Y13-stimulated phosphorylation of CREB is required for ADP-induced proliferation of late developing retinal glial progenitors in culture. Cell Signal. 2017, 35, 95-106. PubMed ID: 28347874
   
   

   The review found that MRS2211 can attenuate ADP-mediated raising in [Ca²⁺]_i in glial cells from cultures at two stages, which suggested the presence of P2Y13 receptors coupled to calcium mobilization in proliferating glial progenitors in culture.

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Reference

1. Pérez-Sen R, et al. (2015). Neuroprotection Mediated by P2Y13 Nucleotide Receptors in Neurons. Comput Struct Biotechnol J. 13, 160-168.

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