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Mol Pharmacol. 2015 Sep;88(3):596-603. doi: 10.1124/mol.115.098764. Epub 2015 May 15.

Model Organisms in G Protein-Coupled Receptor Research.

Author information

1
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.) tobias.langenhan@uni-wuerzburg.de monkk@wustl.edu.
2
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.).

Abstract

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.

PMID:
25979002
PMCID:
PMC4551050
DOI:
10.1124/mol.115.098764
[Indexed for MEDLINE]
Free PMC Article

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