title: PRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome.
abstract: G protein-coupled receptors (GPCRs) are essential mediators of cellular signaling and are important targets of drug action. Of the approximately 350 nonolfactory human GPCRs, more than 100 are still considered to be 'orphans' because their endogenous ligands remain unknown. Here, we describe a unique open-source resource that allows interrogation of the druggable human GPCRome via a G protein-independent β-arrestin-recruitment assay. We validate this unique platform at more than 120 nonorphan human GPCR targets, demonstrate its utility for discovering new ligands for orphan human GPCRs and describe a method (parallel receptorome expression and screening via transcriptional output, with transcriptional activation following arrestin translocation (PRESTO-Tango)) for the simultaneous and parallel interrogation of the entire human nonolfactory GPCRome.
authors.affiliation: 1] Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA. [2] National Institute of Mental Health Psychoactive Drug Screening Program, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Wesley K
authors.initials: WK
authors.lastname: Kroeze
authors.affiliation: 1] Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA. [2] National Institute of Mental Health Psychoactive Drug Screening Program, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Sassano
authors.affiliation: 1] Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA. [2] National Institute of Mental Health Psychoactive Drug Screening Program, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Xi-Ping
authors.initials: XP
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Lansu
authors.affiliation: Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: McCorvy
authors.affiliation: Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Giguère
authors.affiliation: Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Noah
authors.initials: N
authors.lastname: Sciaky
authors.affiliation: 1] Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA. [2] National Institute of Mental Health Psychoactive Drug Screening Program, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA. [3] Program in Neuroscience, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA. [4] Division of Chemical Biology and Medicinal Chemistry, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Roth
mesh_terms: D000595:Amino Acid Sequence; D019390:Arrestins / Q000378:metabolism; D001681:Biological Assay / Q000379:methods*; D006801:Humans; D008024:Ligands; D034622:RNA Interference; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D008024:Ligands; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D000071557:beta-Arrestins