Wauson Eric M, Lorente-Rodríguez Andrés, Cobb Melanie H
Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9041, USA.
Mol Endocrinol. 2013 Aug;27(8):1188-97. doi: 10.1210/me.2013-1100. Epub 2013 Jul 2.
G protein-coupled receptors (GPCRs) are membrane proteins that recognize molecules in the extracellular milieu and transmit signals inside cells to regulate their behaviors. Ligands for many GPCRs are hormones or neurotransmitters that direct coordinated, stereotyped adaptive responses. Ligands for other GPCRs provide information to cells about the extracellular environment. Such information facilitates context-specific decision making that may be cell autonomous. Among ligands that are important for cellular decisions are amino acids, required for continued protein synthesis, as metabolic starting materials and energy sources. Amino acids are detected by a number of class C GPCRs. One cluster of amino acid-sensing class C GPCRs includes umami and sweet taste receptors, GPRC6A, and the calcium-sensing receptor. We have recently found that the umami taste receptor heterodimer T1R1/T1R3 is a sensor of amino acid availability that regulates the activity of the mammalian target of rapamycin. This review focuses on an array of findings on sensing amino acids and sweet molecules outside of neurons by this cluster of class C GPCRs and some of the physiologic processes regulated by them.
G蛋白偶联受体(GPCRs)是膜蛋白,可识别细胞外环境中的分子,并在细胞内传递信号以调节细胞行为。许多GPCRs的配体是激素或神经递质,它们指导协调的、刻板的适应性反应。其他GPCRs的配体向细胞提供有关细胞外环境的信息。此类信息有助于进行可能是细胞自主的特定背景下的决策。对细胞决策很重要的配体包括氨基酸,氨基酸是持续蛋白质合成所需的物质,可作为代谢起始原料和能量来源。多种C类GPCRs可检测氨基酸。一类氨基酸感应C类GPCRs包括鲜味和甜味味觉受体、GPRC6A以及钙敏感受体。我们最近发现,鲜味味觉受体异二聚体T1R1/T1R3是一种氨基酸可用性传感器,可调节雷帕霉素哺乳动物靶蛋白的活性。本综述重点关注关于这一类C类GPCRs在神经元外感知氨基酸和甜味分子的一系列研究结果,以及它们所调节的一些生理过程。