Division of Newborn Medicine, Department of Medicine, Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Current address: Vertex Pharmaceuticals, 50 Northern Avenue, Boston, MA 02210, USA.
Division of Newborn Medicine, Department of Medicine, Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Current address: Sanofi S.A., 49 New York Avenue, Framingham, MA 01701, USA.
Trends Pharmacol Sci. 2019 Apr;40(4):278-293. doi: 10.1016/j.tips.2019.02.003. Epub 2019 Mar 11.
The family of adhesion G protein-coupled receptors (aGPCRs) consists of 33 members in humans. Although the majority are orphan receptors with unknown functions, many reports have demonstrated critical functions for some members of this family in organogenesis, neurodevelopment, myelination, angiogenesis, and cancer progression. Importantly, mutations in several aGPCRs have been linked to human diseases. The crystal structure of a shared protein domain, the GPCR Autoproteolysis INducing (GAIN) domain, has enabled the discovery of a common signaling mechanism - a tethered agonist - for this class of receptors. A series of recent reports has shed new light on their biological functions and disease relevance. This review focuses on these recent advances in our understanding of aGPCR biology in the nervous system and the untapped potential of aGPCRs as novel therapeutic targets for neurological disease.
黏附 G 蛋白偶联受体 (aGPCR) 家族由人类中的 33 个成员组成。尽管大多数是功能未知的孤儿受体，但许多报道表明该家族的某些成员在器官发生、神经发育、髓鞘形成、血管生成和癌症进展中具有关键功能。重要的是，几种 aGPCR 的突变与人类疾病有关。共享蛋白结构域 GPCR 自动蛋白水解诱导 (GAIN) 域的晶体结构，使人们发现了此类受体的一种共同信号机制——连接的激动剂。最近的一系列报告揭示了它们在神经系统中的生物学功能和疾病相关性的新亮点。这篇综述重点介绍了我们对 aGPCR 生物学在神经系统中的理解的最新进展，以及 aGPCR 作为神经疾病新型治疗靶点的未开发潜力。
