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Dissecting the genetic landscape of GPCR signaling through phenotypic profiling in C. elegans

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Listed:
  • Longjun Pu

    (Umeå University
    Umeå University
    Umeå University)

  • Jing Wang

    (Umeå University
    Umeå University
    Umeå University)

  • Qiongxuan Lu

    (Umeå University
    Umeå University
    Umeå University)

  • Lars Nilsson

    (Umeå University
    Umeå University
    Umeå University)

  • Alison Philbrook

    (Brandeis University)

  • Anjali Pandey

    (Brandeis University)

  • Lina Zhao

    (Umeå University
    Umeå University
    Umeå University)

  • Robin van Schendel

    (Leiden University Medical Center)

  • Alan Koh

    (MRC Laboratory of Medical Sciences
    Institute of Clinical Sciences, Imperial College London)

  • Tanara V. Peres

    (MRC Laboratory of Medical Sciences
    Institute of Clinical Sciences, Imperial College London)

  • Weheliye H. Hashi

    (MRC Laboratory of Medical Sciences
    Institute of Clinical Sciences, Imperial College London)

  • Si Lhyam Myint

    (Umeå University
    Umeå University
    Umeå University)

  • Chloe Williams

    (Umeå University)

  • Jonathan D. Gilthorpe

    (Umeå University)

  • Sun Nyunt Wai

    (Umeå University
    Umeå University
    Umeå University)

  • Andre Brown

    (MRC Laboratory of Medical Sciences
    Institute of Clinical Sciences, Imperial College London)

  • Marcel Tijsterman

    (Leiden University Medical Center)

  • Piali Sengupta

    (Brandeis University)

  • Johan Henriksson

    (Umeå University
    Umeå University
    Umeå University)

  • Changchun Chen

    (Umeå University
    Umeå University
    Umeå University)

Abstract

G protein-coupled receptors (GPCRs) mediate responses to various extracellular and intracellular cues. However, the large number of GPCR genes and their substantial functional redundancy make it challenging to systematically dissect GPCR functions in vivo. Here, we employ a CRISPR/Cas9-based approach, disrupting 1654 GPCR-encoding genes in 284 strains and mutating 152 neuropeptide-encoding genes in 38 strains in C. elegans. These two mutant libraries enable effective deorphanization of chemoreceptors, and characterization of receptors for neuropeptides in various cellular processes. Mutating a set of closely related GPCRs in a single strain permits the assignment of functions to GPCRs with functional redundancy. Our analyses identify a neuropeptide that interacts with three receptors in hypoxia-evoked locomotory responses, unveil a collection of regulators in pathogen-induced immune responses, and define receptors for the volatile food-related odorants. These results establish our GPCR and neuropeptide mutant libraries as valuable resources for the C. elegans community to expedite studies of GPCR signaling in multiple contexts.

Suggested Citation

  • Longjun Pu & Jing Wang & Qiongxuan Lu & Lars Nilsson & Alison Philbrook & Anjali Pandey & Lina Zhao & Robin van Schendel & Alan Koh & Tanara V. Peres & Weheliye H. Hashi & Si Lhyam Myint & Chloe Willi, 2023. "Dissecting the genetic landscape of GPCR signaling through phenotypic profiling in C. elegans," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44177-z
    DOI: 10.1038/s41467-023-44177-z
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    References listed on IDEAS

    as
    1. A. J. Venkatakrishnan & Xavier Deupi & Guillaume Lebon & Christopher G. Tate & Gebhard F. Schertler & M. Madan Babu, 2013. "Molecular signatures of G-protein-coupled receptors," Nature, Nature, vol. 494(7436), pages 185-194, February.
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