9ecj

Structural highlights

Function

P2RY8_HUMAN G protein-coupled receptor for S-geranylgeranyl-glutathione (GGG), an endogenous metabolite present in lymphoid tissues. Couples the binding of GGG to the activation of GNA13 and downstream repression of AKT activation in lymphocytes defining their positioning and growth within lymphoid organs (PubMed:25274307, PubMed:30842656, PubMed:34088745). In lymphoid follicles, confines B cells and follicular helper T cells in germinal centers (GCs) in response to GGG local gradients established by GGT5 (via GGG catabolism) and ABCC1 (via extracellular transport) with lower concentrations of GGG found in the follicular dendritic cell network region around which germinal centers are formed (PubMed:25274307, PubMed:30842656, PubMed:34088745). In the bone marrow, also in response to GGG gradients established by GGT5 and ABCC1, it restricts chemotactic transmigration of B cells, T cells and NK cells from blood vessels to the bone marrow parenchyma (PubMed:30842656, PubMed:34088745). Contributes to GNA13-dependent pathway that suppresses GC B cell growth (PubMed:25274307).^{[1] [2] [3]}

References

1. ↑ Muppidi JR, Schmitz R, Green JA, Xiao W, Larsen AB, Braun SE, An J, Xu Y, Rosenwald A, Ott G, Gascoyne RD, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Vaidehi N, Staudt LM, Cyster JG. Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma. Nature. 2014 Dec 11;516(7530):254-8. PMID:25274307 doi:10.1038/nature13765
2. ↑ Lu E, Wolfreys FD, Muppidi JR, Xu Y, Cyster JG. S-Geranylgeranyl-L-glutathione is a ligand for human B cell-confinement receptor P2RY8. Nature. 2019 Mar;567(7747):244-248. PMID:30842656 doi:10.1038/s41586-019-1003-z
3. ↑ Gallman AE, Wolfreys FD, Nguyen DN, Sandy M, Xu Y, An J, Li Z, Marson A, Lu E, Cyster JG. Abcc1 and Ggt5 support lymphocyte guidance through export and catabolism of S-geranylgeranyl-l-glutathione. Sci Immunol. 2021 Jun 4;6(60):eabg1101. PMID:34088745 doi:10.1126/sciimmunol.abg1101