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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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    1. Margarita C. Dinamarca & Adi Raveh & Andy Schneider & Thorsten Fritzius & Simon Früh & Pascal D. Rem & Michal Stawarski & Txomin Lalanne & Rostislav Turecek & Myeongjeong Choo & Valérie Besseyrias & W, 2019. "Complex formation of APP with GABAB receptors links axonal trafficking to amyloidogenic processing," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    2. Cangsong Shen & Chunyou Mao & Chanjuan Xu & Nan Jin & Huibing Zhang & Dan-Dan Shen & Qingya Shen & Xiaomei Wang & Tingjun Hou & Zhong Chen & Philippe Rondard & Jean-Philippe Pin & Yan Zhang & Jianfeng, 2021. "Structural basis of GABAB receptor–Gi protein coupling," Nature, Nature, vol. 594(7864), pages 594-598, June.
    3. Jean-Philippe Pin & Bernhard Bettler, 2016. "Organization and functions of mGlu and GABAB receptor complexes," Nature, Nature, vol. 540(7631), pages 60-68, December.
    4. Hamidreza Shaye & Andrii Ishchenko & Jordy Homing Lam & Gye Won Han & Li Xue & Philippe Rondard & Jean-Philippe Pin & Vsevolod Katritch & Cornelius Gati & Vadim Cherezov, 2020. "Structural basis of the activation of a metabotropic GABA receptor," Nature, Nature, vol. 584(7820), pages 298-303, August.
    5. Masao Doi & Iori Murai & Sumihiro Kunisue & Genzui Setsu & Naohiro Uchio & Rina Tanaka & Sakurako Kobayashi & Hiroyuki Shimatani & Hida Hayashi & Hsu-Wen Chao & Yuuki Nakagawa & Yukari Takahashi & Yun, 2016. "Gpr176 is a Gz-linked orphan G-protein-coupled receptor that sets the pace of circadian behaviour," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    6. Klemens Kaupmann & Katharina Huggel & Jakob Heid & Peter J. Flor & Serge Bischoff & Stuart J. Mickel & Gary McMaster & Christof Angst & Helmut Bittiger & Wolfgang Froestl & Bernhard Bettler, 1997. "Expression cloning of GABAB receptors uncovers similarity to metabotropic glutamate receptors," Nature, Nature, vol. 386(6622), pages 239-246, March.
    7. Carmen Klein Herenbrink & David A. Sykes & Prashant Donthamsetti & Meritxell Canals & Thomas Coudrat & Jeremy Shonberg & Peter J. Scammells & Ben Capuano & Patrick M. Sexton & Steven J. Charlton & Jon, 2016. "The role of kinetic context in apparent biased agonism at GPCRs," Nature Communications, Nature, vol. 7(1), pages 1-14, April.
    8. Jochen Schwenk & Michaela Metz & Gerd Zolles & Rostislav Turecek & Thorsten Fritzius & Wolfgang Bildl & Etsuko Tarusawa & Akos Kulik & Andreas Unger & Klara Ivankova & Riad Seddik & Jim Y. Tiao & Math, 2010. "Native GABAB receptors are heteromultimers with a family of auxiliary subunits," Nature, Nature, vol. 465(7295), pages 231-235, May.
    9. Jinseo Park & Ziao Fu & Aurel Frangaj & Jonathan Liu & Lidia Mosyak & Tong Shen & Vesna N. Slavkovich & Kimberly M. Ray & Jaume Taura & Baohua Cao & Yong Geng & Hao Zuo & Yongjun Kou & Robert Grassucc, 2020. "Author Correction: Structure of human GABAB receptor in an inactive state," Nature, Nature, vol. 583(7818), pages 29-29, July.
    10. Jinseo Park & Ziao Fu & Aurel Frangaj & Jonathan Liu & Lidia Mosyak & Tong Shen & Vesna N. Slavkovich & Kimberly M. Ray & Jaume Taura & Baohua Cao & Yong Geng & Hao Zuo & Yongjun Kou & Robert Grassucc, 2020. "Structure of human GABAB receptor in an inactive state," Nature, Nature, vol. 584(7820), pages 304-309, August.
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