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In diseases such as asthma and chronic obstructive pulmonary disease (COPD), the body produces too much mucus, making breathing difficult. New research from Washington University School of Medicine in St. Louis provides clues to potentially counteract inappropriate mucus production.
"The new study lays the groundwork for developing treatments for diseases such as asthma, COPD, cystic fibrosis and even certain cancers," said senior author Thomas J. Brett, PhD, assistant professor of medicine. "It also solves a 20-year mystery about the role of a protein that has long been associated with these diseases."
The study appears March 17 in the journal eLife.
About two decades ago, the protein CLCA1 was identified. High levels of CLCA1 in cells lining the airway have long been linked with an overproduction of mucus. Studies at the time suggested CLCA1 was an ion channel, a small opening in the cell membrane that allows charged particles to flow into or out of the cell. CLCA1 was labeled a chloride channel because it appeared to be moving chloride ions across the cell membrane. In general, the movement of different ions into and out of cells govern many important processes from mucus production, to heart rhythms to brain function.
"Originally, CLCA1 was misidentified as a chloride channel," Brett said. "When cells express CLCA1, they produce chloride currents. But as we became better at understanding the three-dimensional structures of proteins, researchers in the field started to realize that CLCA proteins couldn't be channels. So the question arose, how do they activate these currents if they're not channels?"
Only seven years ago, a protein that proved to be this elusive type of channel was first discovered in mammals. Called TMEM16A, it is a channel that is ubiquitous in the cells lining the airway. Too much TMEM16A, like elevated levels of CLCA1, were also associated with the mucus-overproduction typical of airway diseases, including asthma and COPD.
The new research now has linked the two, demonstrating that increased expression of CLCA1 increases the number of TMEM16A channels present in nearby cells, according to Brett and his colleagues, including co-authors Colin G. Nichols, PhD, the Carl F. Cori Professor of Cell Biology and Physiology, Monica Sala-Rabanal, PhD, research instructor in medicine, and Zeynep Yurtsever, graduate research assistant.
"We don't think that CLCA1 actually opens the channel," Brett said. "In fact, the channel can function without CLCA1. We think it simply keeps the channel on the surface of the cells for a longer period of time. The reason you get more current is you have more channels there. You're just accumulating more holes for the ions to travel through. This is a unique finding. We don't know of any other examples of this type of interaction between a protein and a channel."
The study also suggests it may be worthwhile to investigate the larger families of these two proteins. If closely related members of these protein families also interact with each other, it could expand the implications to disorders as diverse as cancer and cardiovascular disease.
For example, TMEM16 channels and CLCA proteins have been associated with certain types of cancers including breast tumors that spread to the lungs and in some cardiovascular disorders such as irregular heart rhythms and heart failure, demonstrating a possible broad impact of future work in this area.
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Study sheds new light on asthma, COPD
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HOPE Sheds Light - Part 1: Our Mission
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1,000 farms supply fast food chain KFC with 23 million chickens a year Birds live in huge sheds for just 35 days before they are gassed to death Documentary filmed around 34,000 chickens in a shed with few windows Activists say the conditions the chickens are kept in are 'oppressive' One farmer claims the birds have a short but 'very good life' KFC said all their suppliers meet or exceed UK and EU welfare requirements
By Laura Cox for the Daily Mail
Published: 17:50 EST, 17 March 2015 | Updated: 18:25 EST, 17 March 2015
As one of the UKs most popular fast food chains, it sells almost 400 pieces of chicken every minute.
But now conditions on the farms that supply KFC with 23million chickens a year can be shown for the first time.
The images show tens of thousands of chickens kept together in huge sheds, alive for just 35 days before they are gassed.
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Life on the farm: Supplier Andrew in the shed filled with 34,00 chickens destined for the fast food chain KFC
The thousands of chickens live together in huge sheds for just 35 days before they are gassed
A documentary tonight shows the birds living amid their excrement in conditions activists say are oppressive but the farmer in charge claims its a very good life.
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Witness sheds light on Kenosha shooting
Yona Gavino.
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Witness sheds light on Kenosha shooting - Video
March 16, 2015, 8 a.m.
Railton micro-brewery Seven Sheds invited people to pick hops and reconnect with Tasmania's beer-brewing roots on Saturday.
RAILTON brewery Seven Sheds invited people to pick hops and reconnect with Tasmania's beer-brewing roots on Saturday.
Although the annual hop-picking day attracted fewer people than expected, Seven Sheds owner and brewer Willie Simpson was impressed with the efforts of those who helped harvest the crop.
"To be honest it was very quiet, but we had enough volunteer pickers that we managed to pick all the remaining hops before it started to rain," Mr Simpson said.
HOP TO IT: Cathy and Stephen Kettle joing in the fun of picking hops.
"We actually picked a record harvest of that particular variety."
It is the brewery's eighth year growing hops and this year's pickings will be turned into a single batch Leggett Indian Pale Ale.
The annual harvest attracted a few families, "which was what happened back in the day" Mr Simpson said.
"Families would go and camp for weeks on end and pick the hops," he said.
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Hop crop brews interest in history
The Tsarnaev trial continued Monday at the John Joseph Moakley United States Courthouse with the testimony of three Watertown policemen recounting their experiences from the night of April 18, 2013.
Patrol officer Joseph Reynolds, Sgt. John MacLellan and Sgt. Jeffrey Pugliese testified Monday at the John Joseph Moakley United States Courthouse about their involvement in aconfrontation in Watertown with Boston Marathon bombing suspect Dzhokhar Tsarnaev. PHOTO BY ALEXANDRA WIMLEY/DAILY FREE PRESS STAFF
Dzhokhar Tsarnaev, 21, is charged with 30 federal counts, to which he has pled not guilty. He allegedly placed two bombs at the Boston Marathon finish line in 2013, killing three and injuring more than 260.
Before the officers testimony, jurors in the case were brought to an undisclosed location in South Boston for about 30 minutes to view the boat in which Tsarnaev allegedly hid from law enforcement after the April 18, 2013, shootout in Watertown. The boat, Slipaway II, was placed under three large white tents, and alongside the jurors was suspect Dzhokhar Tsarnaev, who was unshackled and surrounded by security, the Associated Press told media at the trial.
The Slipaway II, previously owned by David and Beth Henneberry of Watertown, was displayed within the boat trailer, which sat elevated in a flatbed. Jurors examined the boat attentively and were elevated in pairs of two by a cage-like device in order to see the details within the boat, the AP reported.
Along the inside of the boat were messages written in pencil, blood streaks and along the bottom were two wooden slats with the message carved stop killing our innocent civilians. At least 110 bullet holes were counted lining all sides of the boat, all of which were marked with evidence tape, they said.
Later on Monday, the officers offered their accounts of the Watertown firefight.
Patrol officer Joseph Reynolds, Sgt. John MacLellan and Sgt. Jeffrey Pugliese
As Reynolds prepared for patrol duty, photos of the alleged Boston Marathon bombers were released. By the time Reynolds reported for roll call, he learned that Massachusetts Institute of Techology police officer Sean Collier had been shot and killed.
At 12:28 a.m., Reynolds said he received the call about a carjacking of a black Mercedes SUV, and was told to be on the lookout for the vehicle. Reynolds started heading toward the reported carjacking and spotted a black Mercedes-Benz on Dexter Street in Watertown. He identified the vehicle as a match to the description and pursued the vehicle from a distance.
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Backyard Sheds for Storage, Comfort and Joy
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