title: EBI2 regulates intracellular signaling and migration in human astrocyte.
abstract: The G protein-coupled receptor EBI2 (Epstein-Barr virus-induced gene 2) is activated by 7α, 25-dihydroxycholesterol (7α25HC) and plays a role in T cell-dependant antibody response and B cell migration. Aberrant EBI2 signaling is implicated in a range of autoimmune disorders however its role in the CNS remains unknown. Here we characterize the functional role of EBI2 in GLIA cells using primary human astrocytes and EBI2 knockout animals. We find human and mouse astrocytes express EBI2 and the enzymes necessary for synthesis and degradation of 7α25HC. In astrocytes, EBI2 activation stimulates ERK phosphorylation, Ca(2+) signaling and induces cellular migration. These results, for the first time, demonstrate a role for EBI2 in astrocyte function and suggest that modulation of this receptor may be beneficial in neuroinflammatory disorders.
authors.affiliation: Drug Development, School of Medicine, Trinity College Dublin, Dublin, Ireland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Rutkowska
authors.forename: Inga
authors.initials: I
authors.lastname: Preuss
authors.forename: Francois
authors.initials: F
authors.lastname: Gessier
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Sailer
authors.forename: Kumlesh K
authors.initials: KK
authors.lastname: Dev
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D019540:Area Under Curve; D001253:Astrocytes / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002454:Cell Differentiation; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology; D002784:Cholesterol / Q000493:pharmacokinetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
chemical_list: C080105:GPR183 protein, human; D005904:Glial Fibrillary Acidic Protein; D043562:Receptors, G-Protein-Coupled; D002784:Cholesterol; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Epstein-Barr virus induced receptor 2 (EBI2); astrocytes; migration; oxysterols; signaling