Pressure-sensitive PIEZO2 protein is essential for reproductive health and internal sensation

2023

Challenge

Sexual function, bladder control, and the movement of food through the digestive system require cells to have the ability to detect mechanical forces. A pressure-sensitive protein called PIEZO2 found in neurons outside the central nervous system is important for sensing gentle touch and the body’s position in space, and it is also involved in a state of pain hypersensitivity called allodynia. However, little is known about PIEZO2’s role in the body’s ability to sense its internal states, nor about what happens to sexual, digestive, and bladder functions when PIEZO2 does not work correctly.

Advance

By studying both people and mice that lack functioning PIEZO2, IRP researchers discovered that loss of the protein results in a constellation of effects that include bladder overfilling, scarring, and urinary urgency; stalled movement of food through the digestive system; and a lack of sensitivity in the genitals that impairs sexual function. In addition, the researchers located the specific classes of neurons that underlie these PIEZO2-related impairments in each of those parts of the body.

Impact

The findings reveal unappreciated roles for specific types of neurons in regulating urination, digestion, and sexual function. In doing so, the study highlights how pharmacologically targeting PIEZO2 may be useful for treating pain and conditions that affect digestion, bladder control, and sexual function. Future studies can now build on the findings to identify the neural circuits in the spinal cord and brain driven by the sorts of neurons identified in the IRP study.

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