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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.
Footnotes
- Received February 28, 2015.
- Accepted May 14, 2015.
This research was supported by the Deutsche Forschungsgemeinschaft [Grants FOR2149/TP1 and TP3 and SFB1047/A5 (to T.L.)], the National Institutes of Health National Institute on Drug Abuse [Exceptional Unconventional Research Enabling Knowledge Acceleration Grant R01-DA037152 (to M.R.B.)], the Fondo Nacional de Desarrollo Científico y Tecnológico [Grant FONDECYT-1141278 (to J.E.)], and the Centro Interdisciplinario de Neurociencia de Valparaiso [Grant P09-022-F (to J.E.)], which is supported by the Millennium Scientific Initiative of the Ministerio de Economía, Fomento y Turismo. This research was also supported by the National Institutes of Health National Institute of Diabetes and Digestive Kidney Diseases [Grants R01-DK059418 and R01-DK074746 (to M.M.B.], the National Institutes of Health National Institute of General Medical Sciences [Grant R01-GM54408 (to L.C.G.)], the National Institutes of Health National Institute of Mental Health [Grant R01-MH067122 (to P.H.T.)], the Intramural Research Program of the National Institutes of Health National Institute of Mental Health [(to B.H.W.)], the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grant R01-NS079445 (to K.R.M.)], and the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development [Grant R01-HD080601 (to K.R.M.)].
- U.S. Government work not protected by U.S. copyright
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