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Cell swelling enhances ligand-driven β-adrenergic signaling

Author

Listed:
  • Alexei Sirbu

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC))

  • Marc Bathe-Peters

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC))

  • Jothi L. M. Kumar

    (University of St Andrews)

  • Asuka Inoue

    (Tohoku University
    Kyoto University)

  • Martin J. Lohse

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
    ISAR Bioscience Institute
    Rudolf-Boehm-Institute of Pharmacology and Toxicology)

  • Paolo Annibale

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
    University of St Andrews)

Abstract

G protein-coupled receptors’ conformational landscape can be affected by their local, microscopic interactions within the cell plasma membrane. We employ here a pleiotropic stimulus, namely osmotic swelling, to alter the cortical environment within intact cells and monitor the response in terms of receptor function and downstream signaling. We observe that in osmotically swollen cells the β2-adrenergic receptor, a prototypical GPCR, favors an active conformation, resulting in cAMP transient responses to adrenergic stimulation that have increased amplitude. The results are validated in primary cell types such as adult cardiomyocytes, a model system where swelling occurs upon ischemia-reperfusion injury. Our results suggest that receptors’ function is finely modulated by their biophysical context, and specifically that osmotic swelling acts as a potentiator of downstream signaling, not only for the β2-adrenergic receptor, but also for other receptors, hinting at a more general regulatory mechanism.

Suggested Citation

  • Alexei Sirbu & Marc Bathe-Peters & Jothi L. M. Kumar & Asuka Inoue & Martin J. Lohse & Paolo Annibale, 2024. "Cell swelling enhances ligand-driven β-adrenergic signaling," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52191-y
    DOI: 10.1038/s41467-024-52191-y
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    References listed on IDEAS

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    1. Roshanak Irannejad & Jin C. Tomshine & Jon R. Tomshine & Michael Chevalier & Jacob P. Mahoney & Jan Steyaert & Søren G. F. Rasmussen & Roger K. Sunahara & Hana El-Samad & Bo Huang & Mark von Zastrow, 2013. "Conformational biosensors reveal GPCR signalling from endosomes," Nature, Nature, vol. 495(7442), pages 534-538, March.
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