How you know when to go: identifying the mechanisms of bladder sensation

2020

Challenge

Urination is one of the primary ways our bodies dispose of waste, but what triggers the need to go? The bladder stretches as it fills and puts pressure on the supporting muscles. However, little is known about how that stretch is detected at the molecular and cellular level and translated into the reflex to urinate.

Advance

Researchers led by IRP senior investigator Alexander T. Chesler, Ph.D., discovered that the PIEZO2 gene, which is critically involved in the sensation of touch and pressure, is also essential for the function of the urinary tract. The team found that people with a rare inherited syndrome caused by non-functional PIEZO2 genes do not feel the urge to urinate until it becomes unpleasantly painful. The research team also demonstrated in mice that when the bladder stretches, the pressure causes proteins encoded by PIEZO2 to open passageways for charged particles to pass through the bladder wall. The researchers then used imaging and behavioral experiments to show that sensation caused by a full bladder is controlled by cells in the bladder wall and nerve cells that function together to stimulate bladder contraction.

Impact

A unique aspect of urination is that all the mechanisms that initiate and sustain urination are driven entirely by mechanical cues such as stretching of the bladder and pressure on the urethra. Yet, until this study, the critical molecules involved in stimulating contraction, as well as the cell types needed to detect these cues, were unknown. These discoveries provide a better understanding of the mechanical process of bladder function and new targets for the development of therapies to treat urinary dysfunction, which affects tens of millions of Americans, particularly women over the age of 50.

Publications

Marshall KL, Saade D, Ghitani N, Coombs AM, Szczot M, Keller J, Ogata T, Daou I, Stowers LT, Bönnemann CG, Chesler AT, Patapoutian A. (2020). PIEZO2 in sensory neurons and urothelial cells coordinates urination. Nature. Dec;588(7837):290-295. doi: 10.1038/s41586-020-2830-7.

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