Regard Jean B, Sato Isaac T, Coughlin Shaun R
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Cell. 2008 Oct 31;135(3):561-71. doi: 10.1016/j.cell.2008.08.040.
G protein-coupled receptors (GPCRs) comprise the largest family of transmembrane signaling molecules and regulate a host of physiological and disease processes. To better understand the functions of GPCRs in vivo, we quantified transcript levels of 353 nonodorant GPCRs in 41 adult mouse tissues. Cluster analysis placed many GPCRs into anticipated anatomical and functional groups and predicted previously unidentified roles for less-studied receptors. From one such prediction, we showed that the Gpr91 ligand succinate can regulate lipolysis in white adipose tissue, suggesting that signaling by this citric acid cycle intermediate may regulate energy homeostasis. We also showed that pairwise analysis of GPCR expression across tissues may help predict drug side effects. This resource will aid studies to understand GPCR function in vivo and may assist in the identification of therapeutic targets.
G蛋白偶联受体(GPCRs)是最大的跨膜信号分子家族,可调节许多生理和疾病过程。为了更好地了解GPCRs在体内的功能,我们对41种成年小鼠组织中的353种非嗅觉GPCRs的转录水平进行了量化。聚类分析将许多GPCRs归入预期的解剖学和功能组,并预测了研究较少的受体以前未被识别的作用。基于这样一个预测,我们发现Gpr91的配体琥珀酸可以调节白色脂肪组织中的脂肪分解,这表明这种柠檬酸循环中间体的信号传导可能调节能量稳态。我们还表明,跨组织的GPCR表达的成对分析可能有助于预测药物副作用。这一资源将有助于了解GPCRs在体内的功能的研究,并可能有助于确定治疗靶点。