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A Scalable, Multiplexed Assay for Decoding GPCR-Ligand Interactions with RNA Sequencing.

Authors
  • Jones, Eric M1
  • Jajoo, Rishi1
  • Cancilla, Daniel1
  • Lubock, Nathan B1
  • Wang, Jeffrey1
  • Satyadi, Megan1
  • Cheung, Rocky1
  • de March, Claire2
  • Bloom, Joshua S3
  • Matsunami, Hiroaki2
  • Kosuri, Sriram4
  • 1 Department of Chemistry and Biochemistry, UCLA-, DOE Institute for Genomics and Proteomics, Molecular Biology Institute, Quantitative and Computational Biology Institute, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, and Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA.
  • 2 Department of Molecular Genetics and Microbiology, and Department of Neurobiology, and Duke Institute for Brain Sciences, Duke University Medical Center, Research Drive, Durham, NC 27710, USA.
  • 3 Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 4 Department of Chemistry and Biochemistry, UCLA-, DOE Institute for Genomics and Proteomics, Molecular Biology Institute, Quantitative and Computational Biology Institute, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, and Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA. Electronic address: [email protected]
Type
Published Article
Journal
Cell systems
Publication Date
Mar 27, 2019
Volume
8
Issue
3
Identifiers
DOI: 10.1016/j.cels.2019.02.009
PMID: 30904378
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

G protein-coupled receptors (GPCRs) are central to how mammalian cells sense and respond to chemicals. Mammalian olfactory receptors (ORs), the largest family of GPCRs, mediate the sense of smell through activation by small molecules, though for most bonafide ligands, they have not been identified. Here, we introduce a platform to screen large chemical panels against multiplexed GPCR libraries using next-generation sequencing of barcoded genetic reporters in stably engineered human cell lines. We mapped 39 mammalian ORs against 181 odorants and identified 79 interactions that have not been reported to our knowledge, including ligands for 15 previously orphaned receptors. This multiplexed receptor assay allows the cost-effective mapping of large chemical libraries to receptor repertoires at scale. Copyright © 2019. Published by Elsevier Inc.

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