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Scientists identify sensor proteins that underlie bladder control




Scientists identify sensor proteins that underlie bladder control

Images of sensory neurons that detect magenta-labeled intravesical signals and cyan-labeled “mechanosensor” protein PIEZO2. Credit: Provided by Adam Coombs.

A team jointly led by Scripps Research scientists has discovered that the key sensor proteins that enable our tactile sensation underlie the sensation that the bladder is full, enabling normal bladder function. did.

Discovered, released on October 14th NatureShows significant advances in basic neurobiology and may also lead to better treatment Management and urination problems that are especially common in the elderly.

“We tend to take urination for granted, which hasn’t been well studied, but if something goes wrong with this system, it’s a big burden,” said Kara, the lead author of the study. Dr. Marshall, a postdoctoral fellow, said. Department of Neuroscience, Scripps Research. “This has identified an important part of how urination works properly.”

Marshall and her colleagues focused on this study on PIEZO2 , A “mechanosensor” that detects the physical elongation of the tissue in which it resides. They found that PIEZO2 was expressed in bladder cells and was required for normal urinary incontinence and functioning in both mice and humans.

“Who would have imagined that the same mechanosensor protein would enable us? Also, do you warn that your bladder is full? “Co-author Dr. Ardem Patapoutian, Professor and President of Neurobiology at the Dorris Neuroscience Center at Scripps Research, and a researcher at the Howard Hughes Medical Institute, said.

In 2010, Patapoutian and his lab first identified PIEZO2 and its sister protein PIEZO1 as mechanosensors that sense mechanical strain in tissues. Because of its feat, Patapoutian, among others, was a co-winner of the prestigious 2020 Kavli Neuroscience Awards.

Like most sensor proteins, PIEZO is an ion channel protein that is embedded in the outer membrane of a host cell and allows charged atoms to flow into the cell when triggered by a stimulus. Sensor ion channel proteins are usually For skin, joints and other organs. In certain neurons, when these channels are fully open to accept the flow of ions, the neuron sends a neural signal to the brain.

In the case of PIEZO, the stimulus that triggers the opening of ion channels is the elongation of the cell membrane by mechanical force on the local tissue. In a study over the last decade, Patapoutian and his colleagues have shown that PIEZO2 is expressed in various organs and tissues throughout the body. For example, they are present in lung tissue to sense lung elongation and help regulate breathing, are present in blood vessels to sense blood pressure, and are present in the skin to mediate tactile sensation.

The new study was a collaboration between Dr. Alexander Chessler, Ph.D., Senior Researcher at the National Institutes of Health and Dr. Karstenbenemann, MD. Chesler, Bönnemann, and their colleagues have studied people born with genetic mutations that result in loss of PIEZO2 function. These individuals suffer from a variety of impaired sensory pathways known to be PIEZO2-related.

In this study, NIH researchers found that these PIEZO2-deficient individuals lacked the usual sensation that their bladder was full, in addition to other sensory disorders. They usually urinate on a schedule to avoid incontinence and struggle to completely empty the bladder when urinating.

Patapoutian, Marshall and colleagues have shown in experiments that PIEZO2 loss has a similar effect in mice. The urethra uses the PIEZO2 protein in both bladder sensory neurons and bladder lining cells called umbrella cells to detect stretch and promote urination. It shows a two-part sensor system. As they have determined experimentally, mouse bladder neurons normally respond tightly to neural signals when the bladder is filled, but in the absence of PIEZO2, they are almost completely silent during bladder filling.

Mice lacking PIEZO2 in the lower urinary tract also showed abnormal micturition reflexes in the muscles that control the urethra through which urine flows from the bladder. This suggests that in mice, and perhaps in people, mechanosensor proteins are required for both normal bladder extension sensation and normal urination.

The team is currently following up on research into the distinct roles of bladder neurons and umbrella cells and how they signal each other. They are also investigating the possible role of other mechanosensors such as PIEZO1 in bladder control and urination.

“Mice without PIEZO2 had obvious dysuria, but were eventually able to urinate, so another mechanosensory protein may be involved,” says Marshall.

Research finds a long-awaited protein sensor for the “sixth sense” — proprioception

For more information:
Kara L. Marshall et al, sensory neurons and urothelial cells PIEZO2 regulate urination, Nature (2020). DOI: 10.1038 / s41586-020-2830-7

Quote: Scientists obtained bladder control on October 14, 2020 from https: // (October 14, 2020) ) Identify the underlying sensor protein

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