Kaczmarek Isabell, Suchý Tomáš, Prömel Simone, Schöneberg Torsten, Liebscher Ines, Thor Doreen
Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, Leipzig University, Johannisallee 30, D-04103 Leipzig, Germany.
Institute of Cell Biology, Heinrich Heine University Düsseldorf, D-40225 Düsseldorf, Germany.
Biol Chem. 2021 Jul 5;403(2):195-209. doi: 10.1515/hsz-2021-0146. Print 2022 Jan 27.
G protein-coupled receptors (GPCRs) modulate a variety of physiological functions and have been proven to be outstanding drug targets. However, approximately one-third of all non-olfactory GPCRs are still orphans in respect to their signal transduction and physiological functions. Receptors of the class of Adhesion GPCRs (aGPCRs) are among these orphan receptors. They are characterized by unique features in their structure and tissue-specific expression, which yields them interesting candidates for deorphanization and testing as potential therapeutic targets. Capable of G-protein coupling and non-G protein-mediated function, aGPCRs may extend our repertoire of influencing physiological function. Besides their described significance in the immune and central nervous systems, growing evidence indicates a high importance of these receptors in metabolic tissue. RNAseq analyses revealed high expression of several aGPCRs in pancreatic islets, adipose tissue, liver, and intestine but also in neurons governing food intake. In this review, we focus on aGPCRs and their function in regulating metabolic pathways. Based on current knowledge, this receptor class represents high potential for future pharmacological approaches addressing obesity and other metabolic diseases.
G蛋白偶联受体（GPCRs）调节多种生理功能，并且已被证明是出色的药物靶点。然而，就其信号转导和生理功能而言，所有非嗅觉GPCRs中约有三分之一仍是孤儿受体。粘附GPCRs（aGPCRs）类受体就属于这些孤儿受体。它们在结构和组织特异性表达方面具有独特特征，这使它们成为孤儿受体解孤儿化以及作为潜在治疗靶点进行测试的有趣候选对象。aGPCRs能够进行G蛋白偶联以及非G蛋白介导的功能，可能会扩展我们影响生理功能的方法。除了它们在免疫和中枢神经系统中已描述的重要性外，越来越多的证据表明这些受体在代谢组织中也非常重要。RNA测序分析显示，几种aGPCRs在胰岛、脂肪组织、肝脏和肠道中高度表达，在控制食物摄入的神经元中也高度表达。在本综述中，我们重点关注aGPCRs及其在调节代谢途径中的功能。基于目前的知识，这类受体在未来针对肥胖症和其他代谢性疾病的药理学方法中具有很高的潜力。
