Nav: Home

Scientists discover the basics of how pressure-sensing Piezo proteins work

August 21, 2019

A team of scientists from Weill Cornell Medicine and The Rockefeller University has illuminated the basic mechanism of Piezo proteins, which function as sensors in the body for mechanical stimuli such as touch, bladder fullness, and blood pressure. The discovery is a feat of basic science that also opens up many new paths of investigation into the roles of Piezo proteins in human diseases and potential new therapeutic strategies.

In the study, published Aug. 21 in Nature, the scientists used advanced microscopy techniques to image the Piezo1 protein at rest and during the application of mechanical forces. They confirmed this complex protein's structure and showed essentially how it can convert mechanical stimuli into an electrical signal.

"Our analysis shows that tension on the cell membrane in which Piezo1 is embedded can flatten and widen the protein's structure," said co-senior author Dr. Simon Scheuring, a professor of physiology and biophysics in anesthesiology at Weill Cornell Medicine. Dr. Scheuring and his laboratory collaborated on the study with the laboratory of Dr. Roderick MacKinnon, a professor of molecular neurobiology and biophysics at The Rockefeller University. Dr. MacKinnon was co-recipient of the Nobel Prize in Chemistry in 2003 for his work determining the structures and mechanisms of ion channel proteins.

Piezo1 and Piezo2 are very large and complex proteins with unique structures. They are embedded within the membranes of certain cell types, and their function is to transduce mechanical force on cells into electrical signals that alter cell activity. Piezo1 proteins work for example in bladder cells to detect when the bladder is full, and in blood vessel-lining cells to detect and help regulate changes in blood pressure. Piezo2 proteins work in sensory nerve endings in the skin and joints, helping to mediate the senses of touch, pain, and proprioception--the sense of how one's limbs are arranged.

Advances in imaging techniques have enabled scientists in recent years to determine the basic structure of Piezo1--a structure that Piezo2 is thought to mostly share. From above this structure has a three-armed, propeller or "triskelion" appearance.

From the side it looks like a shallow bowl embedded in the cell membrane, with an ion channel at its center. The latter, when opened, allows a flow of calcium and other positively charged ions into the cell.

The basic mechanism by which mechanical force opens the ion channel has remained mysterious. But in the new study Dr. Scheuring and Dr. MacKinnon and their colleagues, including lead author Dr. Yi-Chih Lin, a postdoctoral associate in anesthesiology, were able to get a clearer picture of how it works.

They combined cryo-electron microscopy with a less well-known technique called high-speed atomic force microscopy, which produces an image of an object essentially by feeling its surface with a super-sensitive mechanical probe. They showed with these methods that Piezo1 is a springy structure that normally bends the cell membrane where it sits, but will flatten out when, for example, a mechanical force is applied to the cell membrane.

"As the membrane tension increases, the structure of Piezo1 flattens and stretches out to occupy a larger area, which in turn opens the ion channel," Dr. Scheuring said.

He noted the possibility that other stimuli that stretch and flatten the Piezo1 structure, such as a pulling force on its arms from the inside or on an external domain called the CED from the outside the cell, in principle could open the ion channel--making it a suitably versatile mechanism for the wide range of cell types and physiological functions in which it works.

Moreover, given this wide range of cell types--in organs including the lungs, bladder, intestines, and pancreas, as well as in blood vessels and the sensory nervous system--the discovery of the basic Piezo-protein mechanism could lead to new ways of understanding and treating many human diseases. To take one example, Dr. Scheuring said, if the membranes of cells lining blood vessels contain excess cholesterol they would become stiffer, increasing the background tension on embedded Piezo 1 proteins and potentially disrupting these proteins' normal ability to detect and help regulate blood pressure.

"Our finding leads to a great many predictions about Piezo proteins' roles in disease that we and others can now go and investigate," he said.
-end-


Weill Cornell Medicine

Related Science Articles:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.
Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.
Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.
Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.
World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.
PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.
Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.
Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.
More Science News and Science Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.