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PIEZO2 in sensory neurons and urothelial cells coordinates urination

Author

Listed:
  • Kara L. Marshall

    (Dorris Neuroscience Center, The Scripps Research Institute)

  • Dimah Saade

    (National Institutes of Health)

  • Nima Ghitani

    (National Institutes of Health)

  • Adam M. Coombs

    (Dorris Neuroscience Center, The Scripps Research Institute)

  • Marcin Szczot

    (National Institutes of Health)

  • Jason Keller

    (The Scripps Research Institute
    Janelia Research Campus)

  • Tracy Ogata

    (National Institutes of Health)

  • Ihab Daou

    (Dorris Neuroscience Center, The Scripps Research Institute)

  • Lisa T. Stowers

    (The Scripps Research Institute)

  • Carsten G. Bönnemann

    (National Institutes of Health)

  • Alexander T. Chesler

    (National Institutes of Health
    National Institutes of Health)

  • Ardem Patapoutian

    (Dorris Neuroscience Center, The Scripps Research Institute)

Abstract

Henry Miller stated that “to relieve a full bladder is one of the great human joys”. Urination is critically important in health and ailments of the lower urinary tract cause high pathological burden. Although there have been advances in understanding the central circuitry in the brain that facilitates urination1–3, there is a lack of in-depth mechanistic insight into the process. In addition to central control, micturition reflexes that govern urination are all initiated by peripheral mechanical stimuli such as bladder stretch and urethral flow4. The mechanotransduction molecules and cell types that function as the primary stretch and pressure detectors in the urinary tract mostly remain unknown. Here we identify expression of the mechanosensitive ion channel PIEZO2 in lower urinary tract tissues, where it is required for low-threshold bladder-stretch sensing and urethral micturition reflexes. We show that PIEZO2 acts as a sensor in both the bladder urothelium and innervating sensory neurons. Humans and mice lacking functional PIEZO2 have impaired bladder control, and humans lacking functional PIEZO2 report deficient bladder-filling sensation. This study identifies PIEZO2 as a key mechanosensor in urinary function. These findings set the foundation for future work to identify the interactions between urothelial cells and sensory neurons that control urination.

Suggested Citation

  • Kara L. Marshall & Dimah Saade & Nima Ghitani & Adam M. Coombs & Marcin Szczot & Jason Keller & Tracy Ogata & Ihab Daou & Lisa T. Stowers & Carsten G. Bönnemann & Alexander T. Chesler & Ardem Patapout, 2020. "PIEZO2 in sensory neurons and urothelial cells coordinates urination," Nature, Nature, vol. 588(7837), pages 290-295, December.
  • Handle: RePEc:nat:nature:v:588:y:2020:i:7837:d:10.1038_s41586-020-2830-7
    DOI: 10.1038/s41586-020-2830-7
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    Cited by:

    1. Jonathan Madar & Namrata Tiwari & Cristina Smith & Divya Sharma & Shanwei Shen & Alsiddig Elmahdi & Liya Y. Qiao, 2023. "Piezo2 regulates colonic mechanical sensitivity in a sex specific manner in mice," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Clement Verkest & Irina Schaefer & Timo A. Nees & Na Wang & Juri M. Jegelka & Francisco J. Taberner & Stefan G. Lechner, 2022. "Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Nathalia G. Amado & Elena D. Nosyreva & David Thompson & Thomas J. Egeland & Osita W. Ogujiofor & Michelle Yang & Alexandria N. Fusco & Niccolo Passoni & Jeremy Mathews & Brandi Cantarel & Linda A. Ba, 2024. "PIEZO1 loss-of-function compound heterozygous mutations in the rare congenital human disorder Prune Belly Syndrome," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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