GPR50 interacts with neuronal NOGO-A and affects neurite outgrowth.
G protein-coupled receptors (GPCRs) form a link between the cell and their environment when signalling pathways are activated upon ligand binding. However, the ligands and functions for many GPCRs remain to be determined. We sought to understand the function of one such orphan, G protein-coupled receptor 50 (GPR50), through identification of protein interactors. GPR50 was previously discovered as a candidate gene for psychiatric illness and lipid metabolism. Here, we identified neurite outgrowth inhibitor NOGO-A as an interacting partner of GPR50 by yeast two-hybrid studies. We confirmed the interaction in mammalian cells and found an enrichment of both Gpr50 and neuronal Nogo-A at the synapse. In contrast to neuronal NOGO-A overexpression, overexpression of GPR50 increased neurite length and filopodia- and lamellipodia-like structures in differentiated Neuroscreen-1 cells. The results are markedly similar to a recent study in Nogo-A KO mice and support the involvement of GPR50 in mental disorders with links to several disease mechanisms.
Grünewald
Ellen
E
Medical Genetics Section, University of Edinburgh, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh EH42XU, UK. ellen.grunewald@gmail.com
Kinnell
Hazel L
HL
Porteous
David J
DJ
Thomson
Pippa A
PA
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D005260:Female; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000502:physiology* / Q000648:ultrastructure; D000070798:Nogo Proteins; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques
C509754:GPR50 protein, human; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; C000603201:Rtn4 protein, mouse