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!
Make way for the mini flying machines
21.03.2018 | American Chemical Society
New 4-D printer could reshape the world we live in
21.03.2018 | American Chemical Society
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.
In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...
Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...
19.03.2018 | Event News
16.03.2018 | Event News
13.03.2018 | Event News
21.03.2018 | Physics and Astronomy
21.03.2018 | Materials Sciences
21.03.2018 | Life Sciences