GPR105, a novel Gi/o-coupled UDP-glucose receptor expressed on brain glia and peripheral immune cells, is regulated by immunologic challenge: possible role in neuroimmune function.
We have recently shown that UDP-glucose, and some related UDP-sugars, are potent agonists of the novel G protein-coupled receptor GPR105 (recently re-named P2Y(14)). GPR105 is widely expressed throughout many brain regions and peripheral tissues of human and rodents, and couples to a pertussis toxin-sensitive G protein. To further characterise the role of GPR105, we demonstrate by immunohistochemistry with receptor-specific antiserum that GPR105 protein is widely distributed throughout the post mortem human brain where it is localised to glial cells, and specifically co-localises with astrocytes. Using quantitative RT-PCR we also show that GPR105 mRNA exhibits a restricted expression profile in an array of human cell lines and primary cells, with prominent expression detected in immune cells including neutrophils, lymphocytes, and megakaryocytic cells. To investigate the G protein selectivity of GPR105, we used chimeric Galpha subunits (Galpha(qi5), Galpha(qo5), and Galpha(qs5)) and an intracellular Ca(2+) mobilisation assay to demonstrate that GPR105 couples to Galpha subunits of the G(i/o) family but not to G(s) family proteins or to endogenous G(q/11) proteins in HEK-293 cells. Finally, we show that expression of GPR105 mRNA in the rat brain is up-regulated by immunologic challenge with lipopolysaccharide. Based on these observations, we propose that G(i/o)-coupled GPR105 might play an important role in peripheral and neuroimmune function in response to extracellular UDP-sugars.
Moore
Darren J
DJ
Neurobiology Programme, The Babraham Institute, Babraham, Cambridge, CB2 4AT, UK. dmoore20@jhmi.edu
Murdock
Paul R
PR
Watson
Jeannette M
JM
Faull
Richard L M
RL
Waldvogel
Henry J
HJ
Szekeres
Philip G
PG
Wilson
Shelagh
S
Freeman
Katie B
KB
Emson
Piers C
PC
D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism*; D001921:Brain / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D005947:Glucose / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D015213:Neuroimmunomodulation / Q000276:immunology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D058470:Receptors, Purinergic P2Y; D015854:Up-Regulation / Q000276:immunology; D014530:Uridine Diphosphate / Q000276:immunology
D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D005947:Glucose; D008070:Lipopolysaccharides; D021122:Protein Subunits; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic; D018048:Receptors, Purinergic P2; D058470:Receptors, Purinergic P2Y; D014530:Uridine Diphosphate; C518528:P2Y14 receptor, human