Langenhan Tobias, Barr Maureen M, Bruchas Michael R, Ewer John, Griffith Leslie C, Maiellaro Isabella, Taghert Paul H, White Benjamin H, Monk Kelly R
Institute of Physiology, Department of Neurophysiology (T.L.), and Institute of Pharmacology and Toxicology, Rudolf Virchow Center (I.M.), University of Würzburg, Germany, Würzburg, Germany; Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, New Jersey (M.M.B.); Division of Basic Research, Department of Anesthesiology, Washington University Pain Center (M.R.B.), Division of Biological and Biomedical Sciences, Department of Anatomy and Neurobiology (M.R.B., P.H.T.), and Department of Developmental Biology, Hope Center for Neurologic Disorders, (K.R.M.), Washington University School of Medicine, St. Louis, Missouri; Centro Interdisciplinario de Neurociencia, Universidad de Valparaiso, Valparaiso, Chile (J.E.); National Center of Behavioral Genomics, Volen Center for Complex Systems, and Department of Biology, Brandeis University, Waltham, Massachusetts (L.C.G.); and Laboratory of Molecular Biology, National Institutes of Health National Institute of Mental Health, Bethesda, Maryland (B.H.W.)
Institute of Physiology, Department of Neurophysiology (T.L.), and Institute of Pharmacology and Toxicology, Rudolf Virchow Center (I.M.), University of Würzburg, Germany, Würzburg, Germany; Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, New Jersey (M.M.B.); Division of Basic Research, Department of Anesthesiology, Washington University Pain Center (M.R.B.), Division of Biological and Biomedical Sciences, Department of Anatomy and Neurobiology (M.R.B., P.H.T.), and Department of Developmental Biology, Hope Center for Neurologic Disorders, (K.R.M.), Washington University School of Medicine, St. Louis, Missouri; Centro Interdisciplinario de Neurociencia, Universidad de Valparaiso, Valparaiso, Chile (J.E.); National Center of Behavioral Genomics, Volen Center for Complex Systems, and Department of Biology, Brandeis University, Waltham, Massachusetts (L.C.G.); and Laboratory of Molecular Biology, National Institutes of Health National Institute of Mental Health, Bethesda, Maryland (B.H.W.).
Mol Pharmacol. 2015 Sep;88(3):596-603. doi: 10.1124/mol.115.098764. Epub 2015 May 15.
The study of G protein-coupled receptors (GPCRs) has benefited greatly from experimental approaches that interrogate their functions in controlled, artificial environments. Working in vitro, GPCR receptorologists discovered the basic biologic mechanisms by which GPCRs operate, including their eponymous capacity to couple to G proteins; their molecular makeup, including the famed serpentine transmembrane unit; and ultimately, their three-dimensional structure. Although the insights gained from working outside the native environments of GPCRs have allowed for the collection of low-noise data, such approaches cannot directly address a receptor's native (in vivo) functions. An in vivo approach can complement the rigor of in vitro approaches: as studied in model organisms, it imposes physiologic constraints on receptor action and thus allows investigators to deduce the most salient features of receptor function. Here, we briefly discuss specific examples in which model organisms have successfully contributed to the elucidation of signals controlled through GPCRs and other surface receptor systems. We list recent examples that have served either in the initial discovery of GPCR signaling concepts or in their fuller definition. Furthermore, we selectively highlight experimental advantages, shortcomings, and tools of each model organism.
对G蛋白偶联受体（GPCRs）的研究极大地受益于在可控的人工环境中探究其功能的实验方法。在体外开展研究时，GPCR受体学家发现了GPCRs发挥作用的基本生物学机制，包括它们与G蛋白偶联的同名能力；它们的分子组成，包括著名的蛇形跨膜单元；最终还发现了它们的三维结构。尽管在GPCRs的天然环境之外开展研究获得的见解有助于收集低噪声数据，但此类方法无法直接阐明受体的天然（体内）功能。体内研究方法可以补充体外研究方法的严谨性：正如在模式生物中所研究的那样，它对受体作用施加生理限制，从而使研究人员能够推断出受体功能的最显著特征。在此，我们简要讨论一些具体实例，其中模式生物成功地助力阐明了通过GPCRs和其他表面受体系统控制的信号。我们列出了最近在GPCR信号传导概念的初步发现或更全面定义中发挥作用的实例。此外，我们还选择性地强调了每种模式生物的实验优势、缺点和工具。
