Tobias Langenhan, Maureen M Barr, Michael R Bruchas, John Ewer, Leslie C Griffith, Isabella Maiellaro, Paul H Taghert, Benjamin H White, Kelly R Monk

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 biological mechanisms by which GPCRs operate, including their eponymous capacity to couple to G proteins (De Lean et al., 1980), their molecular makeup including the famed serpentine transmembrane unit (Dixon et al., 1986), and ultimately their three-dimensional structure (Palczewski et al., 2000; Rasmussen et al., 2007). While 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 physiological 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. Further, we selectively highlight experimental advantages, shortcomings, and tools of each model organism.