Cloning and Chromosomal Localization of the Human P2Y1 Purinoceptor

Ayyanathan, Kasirajan; Webbs, Tania E.; Sandhu, Arbansjit K.; Athwal, Raghbir S.; Barnard, Eric A.; Kunapuli, Satya P.

doi:10.1006/bbrc.1996.0622

Cited by 29 publications

(43 citation statements)

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“…been examined, it remains feasible that splicing might generate forms that target to two different membrane surfaces in Sertoli cells. By contrast, the gene encoding the P2Y 1 receptor appears to lack introns (Ayyanathan et al, 1996), suggesting that this receptor does not undergo alternative splicing.…”

Section: Discussionmentioning

confidence: 96%

Charged residues in the C-terminus of the P2Y1 receptor constitute a basolateral-sorting signal

Wolff

Harden

et al. 2010

Journal of Cell Science

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SummaryThe P2Y 1 receptor is localized to the basolateral membrane of polarized Madin-Darby canine kidney (MDCK) cells. In the present study, we identified a 25-residue region within the C-terminal tail (C-tail) of the P2Y 1 receptor that directs basolateral sorting. Deletion of this sorting signal caused redirection of the receptor to the apical membrane, indicating that the region from the N-terminus to transmembrane domain 7 (TM7) contains an apical-sorting signal that is overridden by a dominant basolateral signal in the C-tail. Location of the signal relative to TM7 is crucial, because increasing its distance from the end of TM7 resulted in loss of basolateral sorting. The basolateral-sorting signal does not use any previously established basolateral-sorting motifs, i.e. tyrosine-containing or dihydrophobic motifs, for function, and it is functional even when inverted or when its amino acids are scrambled, indicating that the signal is sequence independent. Mutagenesis of different classes of amino acids within the signal identified charged residues (five basic and four acidic amino acids in 25 residues) as crucial determinants for sorting function, with amidated amino acids having a lesser role. Mutational analyses revealed that whereas charge balance (+1 overall) of the signal is unimportant, the total number of charged residues (nine), either positive or negative, is crucial for basolateral targeting. These data define a new class of targeting signal that relies on total charge and might provide a common mechanism for polarized trafficking of epithelial proteins.

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Section: Discussionmentioning

confidence: 96%

Charged residues in the C-terminus of the P2Y1 receptor constitute a basolateral-sorting signal

Wolff

Harden

et al. 2010

Journal of Cell Science

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“…The P2 family is divided into two main types as follows: the P2X receptors are ligand-gated ion channels, and the P2Y receptors are G protein-coupled [15,16] . P2Y 1 is the first member of the P2Y family to be identified and is widely distributed in various tissues [17][18][19] . Astrocytes have multiple functions in the brain and are the predominant neuroglial cells of the CNS.…”

Section: Discussionmentioning

confidence: 99%

Effects of P2Y1 receptor on glial fibrillary acidic protein and glial cell line-derived neurotrophic factor production of astrocytes under ischemic condition and the related signaling pathways

Sun

Liu

2008

Neurosci. Bull.

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Objective The present study aimed to explore the role of P2Y 1 receptor in glial fibrillary acidic protein (GFAP) production and glial cell line-derived neurotrophic factor (GDNF) secretion of astrocytes under ischemic insult and the related signaling pathways. Methods Using transient right middle cerebral artery occlusion (tMCAO) and oxygen-glucose-serum deprivation for 2 h as the model of ischemic injury in vivo and in vitro, immunofluorescence, quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, enzyme linked immunosorbent assay (ELISA) were used to investigate location of P2Y 1 receptor and GDNF, the expression of GFAP and GDNF, and the changes of signaling molecules. Results Blockage of P2Y 1 receptor with the selective antagonist N 6 -methyl-2'-deoxyadenosine 3',5'-bisphosphate diammonium (MRS2179) reduced GFAP production and increased GDNF production in the antagonist group as compared with simple ischemic group both in vivo and in vitro. Oxygen-glucose-serum deprivation and blockage of P2Y 1 receptor caused elevation of phosphorylated Akt and cAMP response element binding protein (CREB), and reduction of phosphorylated Janus kinase2 (JAK2) and signal transducer and activator of transcription3 (STAT3, Ser727). After blockage of P2Y 1 receptor and deprivation of oxygen-glucose-serum, AG490 (inhibitor of JAK2) reduced phosphorylation of STAT3 (Ser727) as well as expression of GFAP; LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3-K), decreased phosphorylation of Akt and CREB; the inhibitor of mitogen-activated protein kinase kinase1/2 (MEK1/2) U0126, an important molecule of Ras/extracellular signalregulated kinase (ERK) signaling pathway, decreased the phosphorylation of JAK2, STAT3 (Ser727), Akt and CREB. Conclusion These results suggest that P2Y 1 receptor plays a role in the production of GFAP and GDNF in astrocytes under transient ischemic condition and the related signaling pathways may be JAK2/STAT3 and PI3-K/Akt/CREB, respectively, and that crosstalk probably exists between them.

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“…P2Y 1 receptor expression presented a multiple band pattern: a band of 42 kDa that corresponds to the P2Y 1 receptor monomer [42] and additional bands with molecular weights of 90 and 266 kDa. Similar bands were previously described and may represent homomeric forms of the P2Y 1 receptor, or heteromers with A 1 receptors [43][44][45].…”

Section: Methyl-[mentioning

confidence: 99%

P2Y receptors on astrocytes and microglia mediate opposite effects in astroglial proliferation

Quintas

Fraga

Gonçalves

et al. 2011

Purinergic Signalling

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Nucleotides released upon brain injury signal to astrocytes and microglia playing an important role in astrogliosis, but the participation of microglia in the purinergic modulation of astrogliosis is still unclear. Highly enriched astroglial cultures and co-cultures of astrocytes and microglia were used to investigate the influence of microglia in the modulation of astroglial proliferation mediated by nucleotides. In highly enriched astroglial cultures, adenosine-5'-triphosphate (ATP), adenosine 5'-O-(3-thio)-triphosphate (ATPγS), adenosine 5'-O-(3-thio)-diphosphate (ADPβS; 0.01-1 mM), and adenosine-5'-diphosphate (ADP; 0.1-1 mM) increased proliferation up to 382%, an effect abolished in co-cultures containing 8% of microglia. The loss of ATP proliferative effect in co-cultures is supported by its fast metabolism and reduced ADP accumulation, an agonist of P2Y 1,12 receptors that mediate astroglial proliferation. No differences in ADPβS and ATPγS metabolism or P2Y 1,12 receptors expression were found in co-cultures that could explain the loss of their proliferative effect. However, conditioned medium from microglia cultures or co-cultures treated with ADPβS, when tested in highly enriched astroglial cultures, also prevented ADPβS proliferative effect. None of the uracil nucleotides tested had any effect in proliferation of highly enriched astroglial cultures, but uridine-5′-triphosphate (UTP; 0.1-1 mM) inhibited proliferation up to 66% in co-cultures, an effect that was dependent on uridine-5'-diphosphate (UDP) accumulation, coincident with a co-localization of P2Y 6 receptors in microglia and due to cell apoptosis. The results indicate that microglia control astroglial proliferation by preventing the proliferative response to adenine nucleotides and favouring an inhibitory effect of UTP/UDP. Several microglial P2Y receptors may be involved by inducing the release of messengers that restrain astrogliosis, a beneficial effect for neuronal repair mechanisms following brain injury.

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Cloning and Chromosomal Localization of the Human P2Y1 Purinoceptor

Cited by 29 publications

References 0 publications

Charged residues in the C-terminus of the P2Y1 receptor constitute a basolateral-sorting signal

Charged residues in the C-terminus of the P2Y1 receptor constitute a basolateral-sorting signal

Effects of P2Y1 receptor on glial fibrillary acidic protein and glial cell line-derived neurotrophic factor production of astrocytes under ischemic condition and the related signaling pathways

P2Y receptors on astrocytes and microglia mediate opposite effects in astroglial proliferation

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