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Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons

Author

Listed:
  • Chanjuan Xu

    (Huazhong University of Science and Technology
    Guangzhou Regenerative Medicine and Health Guangdong Laboratory)

  • Yiwei Zhou

    (Huazhong University of Science and Technology
    Kindstar Global Precision Medicine Institute)

  • Yuxuan Liu

    (Huazhong University of Science and Technology)

  • Li Lin

    (Huazhong University of Science and Technology)

  • Peng Liu

    (Huazhong University of Science and Technology)

  • Xiaomei Wang

    (Huazhong University of Science and Technology)

  • Zhengyuan Xu

    (Huazhong University of Science and Technology)

  • Jean-Philippe Pin

    (Université de Montpellier, CNRS, INSERM)

  • Philippe Rondard

    (Université de Montpellier, CNRS, INSERM)

  • Jianfeng Liu

    (Huazhong University of Science and Technology
    Guangzhou Regenerative Medicine and Health Guangdong Laboratory)

Abstract

G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins and are important drug targets. The discovery of drugs targeting these receptors and their G protein signaling properties are based on assays mainly performed with modified receptors expressed in heterologous cells. However, GPCR responses may differ in their native environment. Here, by using highly sensitive Gi/o sensors, we reveal specific properties of Gi/o protein-mediated responses triggered by GABAB, α2 adrenergic and cannabinoid CB1 receptors in primary neurons, different from those in heterologous cells. These include different profiles in the Gi/o protein subtypes-mediated responses, and differences in the potencies of some ligands even at similar receptor expression levels. Altogether, our results show the importance of using biosensors compatible with primary cells for evaluating the activities of endogenous GPCRs in their native environment.

Suggested Citation

  • Chanjuan Xu & Yiwei Zhou & Yuxuan Liu & Li Lin & Peng Liu & Xiaomei Wang & Zhengyuan Xu & Jean-Philippe Pin & Philippe Rondard & Jianfeng Liu, 2024. "Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46177-z
    DOI: 10.1038/s41467-024-46177-z
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    References listed on IDEAS

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