Cell size is regulated by the balance of positively and negatively charged ions and other solutes in the fluid inside and outside cells, which in turn prevents water from moving across cell membranes and changing cell size. Changes in chemical composition of extracellular fluid can disrupt this balance, sometimes with damaging consequences to health.
"If you eat a bag of salty potato chips or a jug of water, the cells lining your stomach will be under pressure to shrink or expand," explains Richard Lifton, senior author of the paper and Sterling Professor of Genetics and Internal Medicine. "Cells need to rapidly change their ionic composition to compensate and avoid blowing up like balloons or shrinking like raisins, and they do this by almost instantly changing their chloride levels."
In the Aug. 7 issue of the journal Cell, a team of Yale scientists led by Jesse Rinehart, associate research scientist in genetics and Lifton, an investigator of the Howard Hughes Medical Institute, report they used innovative new quantitative proteomics technologies to identify two key regulatory transporter sites that control the exit of potassium and chloride out of cells.
The proteomics technologies allow scientists to observe specific sites on proteins that undergo phosphorylation. Phosphorylation is a common and reversible modification made to a protein after it is synthesized and can turn a protein's function on or off. The Yale scientists show that the regulatory sites they identified are almost completely phosphorylated under normal conditions, when the transporter is inactive. When confronted with changes in the environment that challenge the cell, the proteins are rapidly dephosphorylated and dramatically increase transport activity.
"These transporters are overactive in sickle cell anemia and play a role in the dehydration of sickle cells," said Patrick Gallagher, professor of pediatrics at the Yale School of Medicine and a co-author of the study. "With this new information, we may be able to find new strategies to manipulate this activity and identify new treatments that are so urgently needed."
Gallagher's lab is already studying genetic variations in the potassium-chloride pathway in a search of new drug targets.
This same system also helps regulate how brain cells respond to the neurotransmitter GABA, which governs wakefulness and has been implicated in anxiety and other disorders, Lifton said. The investigators found that phosphorylation of the regulatory sites worked the same way in the brain.
Looking to the future, Rinehart speculated that application of these new technologies will prove to be relevant to understanding many other biological regulatory systems.
The study was funded by the National Institutes of Health and the Leducq Foundation.
Other Yale authors of the research were Yelena D. Maksimova, Jessica E. Tanis, Kathryn L. Stone, Caleb A. Hodson, Junhui Zhang, Weijun Pan, Dianqing Wu, Christopher M. Colangelo, Biff Forbush, Erol E. Gulcicek
Bill Hathaway | EurekAlert!
The birth of a new protein
20.10.2017 | University of Arizona
Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research