Researchers at the Victor Chang Cardiac Institute have identified a molecule that plays a key role in how cells sense when they are being pushed or pulled which could lead to the development of future drugs for obesity, osteoporosis, and inflammatory diseases.
The researchers believe it will now be possible to design new therapeutics that could either ramp down or dial down the activity of the sensors, also known as PIEZO ion channels. The findings are published in Science in an article titled, “MyoD-family inhibitor proteins act as auxiliary subunits of Piezo channels.”
“Piezo channels are critical cellular sensors of mechanical forces,” wrote the researchers. “Despite their large size, ubiquitous expression, and irreplaceable roles in an ever-growing list of physiological processes, few Piezo channel–binding proteins have emerged. In this work, we found that MyoD (myoblast determination)–family inhibitor proteins (MDFIC and MDFI) are PIEZO1/2 interacting partners.”
“These are really key molecules that constantly provide information to the brain such as where our bodies are in space, sensing touch and even pain,” said lead author Charles Cox, PhD.
“This interacting molecule we have identified represents a switch enabling us to regulate these channels, widely expressed throughout the body, which is why it could be useful for a whole range of diseases in the future.”
Cox and his collaborators used cryo-electron microscopy to find out how this protein binds to PIEZO ion channels.
“We believe we will be able to boost the activity in the channels that are involved in the strength of our bones—which could not only help prevent osteoporosis it could help those already suffering,” Cox added.
“This novel mechanism could also help combat obesity an important risk factor for all cardiovascular diseases. As we eat food, our stomachs get stretched and molecules are triggered, telling the brain when the stomach is full. By boosting the activity of these molecules, we may be able to trigger the brain into thinking it was full far earlier mimicking satiety.”
The researchers believe the molecule could also be adapted to target inflammatory diseases as well as cardiovascular disease in the future.