Journal article
PIEZO2 in sensory neurons and urothelial cells coordinates urination
Nature (London), Vol.588(7837), pp.290-295
12/2020
DOI: 10.1038/s41586-020-2830-7
PMCID: PMC7725878
PMID: 33057202
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 urination
, 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 flow
. 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.
Details
- Title: Subtitle
- PIEZO2 in sensory neurons and urothelial cells coordinates urination
- Creators
- Kara L Marshall - Scripps Research InstituteDimah Saade - National Institute of Neurological Disorders and StrokeNima Ghitani - National Center for Complementary and Integrative HealthAdam M Coombs - Scripps Research InstituteMarcin Szczot - National Center for Complementary and Integrative HealthJason Keller - Scripps Research InstituteTracy Ogata - National Institute of Neurological Disorders and StrokeIhab Daou - Scripps Research InstituteLisa T Stowers - Scripps Research InstituteCarsten G Bönnemann - National Institute of Neurological Disorders and StrokeAlexander T Chesler - National Institute of Neurological Disorders and StrokeArdem Patapoutian - Scripps Research Institute
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.588(7837), pp.290-295
- DOI
- 10.1038/s41586-020-2830-7
- PMID
- 33057202
- PMCID
- PMC7725878
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Grant note
- R35 NS105067 / NINDS NIH HHS R01 NS108439 / NINDS NIH HHS Z99 AT999999 / Intramural NIH HHS Howard Hughes Medical Institute F32 DK121494 / NIDDK NIH HHS
- Language
- English
- Date published
- 12/2020
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984353935102771
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