Medical Genetics Section, University of Edinburgh, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh EH42XU, UK.
Mol Cell Neurosci. 2009 Dec;42(4):363-71. doi: 10.1016/j.mcn.2009.08.007. Epub 2009 Aug 21.
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.
G 蛋白偶联受体 (GPCRs) 在配体结合后激活信号通路时，在细胞与其环境之间建立联系。然而，许多 GPCR 的配体和功能仍有待确定。我们试图通过鉴定蛋白质相互作用体来了解一种孤儿 G 蛋白偶联受体 50 (GPR50) 的功能。GPR50 先前被发现是精神疾病和脂质代谢的候选基因。在这里，我们通过酵母双杂交研究发现神经突生长抑制剂 NOGO-A 是 GPR50 的相互作用伙伴。我们在哺乳动物细胞中证实了这种相互作用，并发现 Gpr50 和神经元 Nogo-A 在突触处富集。与神经元 NOGO-A 过表达相反，GPR50 的过表达增加了分化的 Neuroscreen-1 细胞中的神经突长度和丝状伪足和片状伪足样结构。这些结果与最近在 Nogo-A KO 小鼠中的一项研究非常相似，支持 GPR50 参与与多种疾病机制相关的精神障碍。
