The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells
Files
Publication date
2016-05-24
Authors
Chang, Gin Wen
Hsiao, Cheng Chih
Peng, Yen Ming
Vieira Braga, Felipe A.
Kragten, Natasja A M
Remmerswaal, Ester B M
van de Garde, Martijn D B
Straussberg, Rachel
König, Gabriele M.
Kostenis, Evi
Editors
Advisors
Supervisors
Document Type
Article
Metadata
Show full item recordCollections
License
cc_by_nc_nd
Abstract
Natural killer (NK) cells possess potent cytotoxic mechanisms that need to be tightly controlled. Here, we explored the regulation and function of GPR56/ADGRG1, an adhesion G protein-coupled receptor implicated in developmental processes and expressed distinctively in mature NK cells. Expression of GPR56 was triggered by Hobit (a homolog of Blimp-1 in T cells) and declined upon cell activation. Through studying NK cells from polymicrogyria patients with disease-causing mutations in ADGRG1, encoding GPR56, and NK-92 cells ectopically expressing the receptor, we found that GPR56 negatively regulates immediate effector functions, including production of inflammatory cytokines and cytolytic proteins, degranulation, and target cell killing. GPR56 pursues this activity by associating with the tetraspanin CD81. We conclude that GPR56 inhibits natural cytotoxicity of human NK cells.
Keywords
Adhesion GPCRs, Cytotoxicity, Immune regulation, NK cells, Transcription factor, General Biochemistry,Genetics and Molecular Biology, Journal Article
Citation
Chang, G W, Hsiao, C C, Peng, Y M, Vieira Braga, F A, Kragten, N A M, Remmerswaal, E B M, van de Garde, M D B, Straussberg, R, König, G M, Kostenis, E, Knäuper, V, Meyaard, L, van Lier, R A W, van Gisbergen, K P J M, Lin, H H & Hamann, J 2016, 'The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells', Cell Reports [E], vol. 15, no. 8, pp. 1757-1770. https://doi.org/10.1016/j.celrep.2016.04.053