Wanka Lizzy, Behr Victoria, Beck-Sickinger Annette G
Institute of Biochemistry, Faculty of Life Sciences, Leipzig University, Brüderstr. 34, D-04103 Leipzig, Germany.
Biol Chem. 2021 May 26;403(2):133-149. doi: 10.1515/hsz-2021-0128. Print 2022 Jan 27.
The internalization of G protein-coupled receptors (GPCRs) is an important mechanism regulating the signal strength and limiting the opportunity of receptor activation. Based on the importance of GPCRs, the detailed knowledge about the regulation of signal transduction is crucial. Here, current knowledge about the agonist-induced, arrestin-dependent internalization process of rhodopsin-like GPCRs is reviewed. Arrestins are conserved molecules that act as key players within the internalization process of many GPCRs. Based on highly conserved structural characteristics within the rhodopsin-like GPCRs, the identification of arrestin interaction sites in model systems can be compared and used for the investigation of internalization processes of other receptors. The increasing understanding of this essential regulation mechanism of receptors can be used for drug development targeting rhodopsin-like GPCRs. Here, we focus on the neuropeptide Y receptor family, as these receptors transmit various physiological processes such as food intake, energy homeostasis, and regulation of emotional behavior, and are further involved in pathophysiological processes like cancer, obesity and mood disorders. Hence, this receptor family represents an interesting target for the development of novel therapeutics requiring the understanding of the regulatory mechanisms influencing receptor mediated signaling.
G蛋白偶联受体（GPCRs）的内化是一种调节信号强度和限制受体激活机会的重要机制。鉴于GPCRs的重要性，深入了解信号转导的调控机制至关重要。在此，我们综述了目前关于视紫红质样GPCRs激动剂诱导的、依赖抑制蛋白的内化过程的相关知识。抑制蛋白是一类保守分子，在许多GPCRs的内化过程中起着关键作用。基于视紫红质样GPCRs高度保守的结构特征，在模型系统中鉴定抑制蛋白相互作用位点，并将其用于研究其他受体的内化过程。对受体这一重要调控机制的深入理解可用于开发靶向视紫红质样GPCRs的药物。在此，我们重点关注神经肽Y受体家族，因为这些受体传递多种生理过程，如食物摄入、能量稳态和情绪行为调节，并且还参与癌症、肥胖和情绪障碍等病理生理过程。因此，这个受体家族是开发新型治疗药物的一个有吸引力的靶点，这需要了解影响受体介导信号传导的调控机制。
