PIEZO2 in sensory neurons and urothelial cells coordinates urination

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 () and Ardem Patapoutian ()
Additional contact information
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
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
Ardem Patapoutian: Dorris Neuroscience Center, The Scripps Research Institute

Nature, 2020, vol. 588, issue 7837, 290-295

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41586-020-2830-7

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