RGD Reference Report - UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis.

Authors: Koizumi, Schuichi  Shigemoto-Mogami, Yukari  Nasu-Tada, Kaoru  Shinozaki, Yoichi  Ohsawa, Keiko  Tsuda, Makoto  Joshi, Bhalchandra V  Jacobson, Kenneth A  Kohsaka, Shinichi  Inoue, Kazuhide 
Citation: Koizumi S, etal., Nature. 2007 Apr 26;446(7139):1091-5. doi: 10.1038/nature05704. Epub 2007 Apr 4.
RGD ID: 13673830
Pubmed: PMID:17410128   (View Abstract at PubMed)
PMCID: PMC3464483   (View Article at PubMed Central)
DOI: DOI:10.1038/nature05704   (Journal Full-text)

Microglia, brain immune cells, engage in the clearance of dead cells or dangerous debris, which is crucial to the maintenance of brain functions. When a neighbouring cell is injured, microglia move rapidly towards it or extend a process to engulf the injured cell. Because cells release or leak ATP when they are stimulated or injured, extracellular nucleotides are thought to be involved in these events. In fact, ATP triggers a dynamic change in the motility of microglia in vitro and in vivo, a previously unrecognized mechanism underlying microglial chemotaxis; in contrast, microglial phagocytosis has received only limited attention. Here we show that microglia express the metabotropic P2Y6 receptor whose activation by endogenous agonist UDP triggers microglial phagocytosis. UDP facilitated the uptake of microspheres in a P2Y6-receptor-dependent manner, which was mimicked by the leakage of endogenous UDP when hippocampal neurons were damaged by kainic acid in vivo and in vitro. In addition, systemic administration of kainic acid in rats resulted in neuronal cell death in the hippocampal CA1 and CA3 regions, where increases in messenger RNA encoding P2Y6 receptors that colocalized with activated microglia were observed. Thus, the P2Y6 receptor is upregulated when neurons are damaged, and could function as a sensor for phagocytosis by sensing diffusible UDP signals, which is a previously unknown pathophysiological function of P2 receptors in microglia.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
P2ry6Ratcellular response to pyrimidine ribonucleotide involved_inIMP PMID:17410128ARUK-UCL 
Itgb1Ratphagocytosis involved_inIMP PMID:17410128ARUK-UCL 
P2ry6Ratphagocytosis involved_inIMP PMID:17410128ARUK-UCL 
P2ry6Ratpositive regulation of release of sequestered calcium ion into cytosol involved_inIMP PMID:17410128ARUK-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Itgb1  (integrin subunit beta 1)
P2ry6  (pyrimidinergic receptor P2Y6)


Additional Information