PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Team solves decades-old mystery of how cells keep from bursting

The findings may lead to new insights into immune deficiency, stroke and diabetes

2014-04-10
(Press-News.org) LA JOLLA, CA—April 10, 2014—A team led by scientists at The Scripps Research Institute (TSRI) has identified a long-sought protein that facilitates one of the most basic functions of cells: regulating their volume to keep from swelling excessively.

The identification of the protein, dubbed SWELL1, solves a decades-long mystery of cell biology and points to further discoveries about its roles in health and disease—including a serious immune deficiency that appears to result from its improper function.

"Knowing the identity of this protein and its gene opens up a broad new avenue of research," said the study's principal investigator Ardem Patapoutian, a Howard Hughes Medical Institute (HHMI) Investigator and professor at TSRI's Dorris Neuroscience Center and Department of Molecular and Cellular Neuroscience.

The report appears as the cover story in the April 10, 2014 issue of the journal Cell.

Unraveling the Mystery

Water passes through the membrane of most cells with relative ease and tends to flow in a direction that evens out the concentration of dissolved molecules or "solutes." "Water in effect follows the solutes," explained Zhaozhu Qiu, a member of the Patapoutian laboratory who was first author of the study. "Any decrease in the solute concentration outside a cell or an increase within the cell will make the cell swell with water."

For decades, experiments have demonstrated the existence of a key relief valve for this swelling: an unidentified ion channel in the cell membrane, dubbed VRAC (volume-regulated anion channel). VRAC opens in response to cell swelling and permits an outflow of chloride ions and some other negatively charged molecules—which water molecules follow, thus reducing the swelling.

"For the past 30 years, scientists have known that there is this VRAC channel, and yet they haven't known its molecular identity," said Patapoutian.

Finding the proteins that make VRAC and their genes was a goal that had eluded prior attempts because of the technical hurdles involved. However, in the new study, Qiu and his colleagues were able to set up a rapid, "high-throughput" screening test based on fluorescence. They engineered human cells to produce a fluorescent protein whose glow would be quenched when the cells became swollen and VRAC channels opened.

With the help of automated screening specialists at the La Jolla-based Genomics Institute of the Novartis Research Foundation (GNF), which recently began a broad new collaboration agreement with TSRI, the team cultured large arrays of the cells and, using a technique known as RNA interference, blocked the activity of a different gene for each clump of cells.

The idea was to watch for the groups of cells that continued to glow—indicating that the gene inactivation had disrupted VRAC.

In this way, with several rounds of tests, the team sifted through the human genome and ultimately found one gene whose disruption reliably terminated VRAC activity. It was a gene that had been discovered in 2003 and catalogued as "LRRC8." Although it appeared to code for a cell-membrane-spanning protein—as one would expect for an ion channel—almost nothing else was known about it. The team renamed it SWELL1.

Potential Roles in Disease

Investigating further, the researchers showed that SWELL1 does indeed localize to the cell membrane as an ion channel protein would. Experiments by Adrienne Dubin, a staff scientist at TSRI, showed that certain mutations of SWELL1 alter the VRAC channel's ion-passing properties—indicating that SWELL1 is a central feature of the ion channel itself.

"It is at least a major part of the VRAC channel for which cell biologists have been searching all this time," said Patapoutian.

Patapoutian, Qiu and their colleagues now will study SWELL1 further, including an examination of what happens to lab mice that lack the protein in various cell types.

Curiously, the gene for SWELL1 was first noted by scientists because a mutant, dysfunctional form of it causes a very rare type of agammaglobulinemia—a lack of antibody-producing B cells, which leaves a person unusually vulnerable to infections. That suggests that SWELL1 is somehow required for normal B-cell development.

"There also have been suggestions from prior studies that this volume-sensitive ion channel is involved in stroke because of the brain-tissue swelling associated with stroke and that it may be involved as well in the secretion of insulin by pancreatic cells," said Patapoutian. "So there are lots of hints out there about its relevance to disease—we just have to go and figure it all out now."

INFORMATION:Other co-authors of the study, "SWELL1, a plasma membrane protein, is an essential component of volume-regulated anion channel," were Jayanti Mathur, Buu Tu, Kritika Reddy, Loren J. Miraglia and Anthony P. Orth of GNF, and Jürgen Reinhardt of the Novartis Institutes for Biomedical Research in Basel, Switzerland.

The research was supported by the National Institutes of Health (grant R01 DE022115).


ELSE PRESS RELEASES FROM THIS DATE:

Lactate metabolism target halts growth in lung cancer model

2014-04-10
BOSTON – Cancer cells generate energy differently than normal cells, a characteristic that helps them to survive and metastasize. A major goal in the field of cancer metabolism is to find ways to overcome this survival advantage. Now a research team led by investigators in the Cancer Center at Beth Israel Deaconess Medical Center (BIDMC) has found that targeting the enzyme responsible for the final step of glucose metabolism not only halts tumor growth in non-small-cell lung cancer, but actually leads to the regression of established tumors. Importantly, the new findings, ...

Getting to the root of Parkinson's disease

2014-04-10
Working with human neurons and fruit flies, researchers at Johns Hopkins have identified and then shut down a biological process that appears to trigger a particular form of Parkinson's disease present in a large number of patients. A report on the study, in the April 10 issue of the journal Cell, could lead to new treatments for this disorder. "Drugs such as L-dopa can, for a time, manage symptoms of Parkinson's disease, but as the disease worsens, tremors give way to immobility and, in some cases, to dementia. Even with good treatment, the disease marches on," says ...

Too much protein may kill brain cells as Parkinson's progresses

Too much protein may kill brain cells as Parkinsons progresses
2014-04-10
Scientists may have discovered how the most common genetic cause of Parkinson's disease destroys brain cells and devastates many patients worldwide. The study was partially funded by the National Institutes of Health's National Institute of Neurological Disorders and Stroke (NINDS); the results may help scientists develop new therapies. "This may be a major discovery for Parkinson's disease patients," said Ted Dawson, M.D., Ph.D., director of the Johns Hopkins University (JHU) Morris K. Udall Center of Excellence for Parkinson's Disease, Baltimore, MD. Dr. Dawson and ...

Researchers determine how mechanical forces affect T-cell recognition and signaling

Researchers determine how mechanical forces affect T-cell recognition and signaling
2014-04-10
T-cells are the body's sentinels, patrolling every corner of the body in search of foreign threats such as bacteria and viruses. Receptor molecules on the T-cells identify invaders by recognizing their specific antigens, helping the T-cells discriminate attackers from the body's own cells. When they recognize a threat, the T-cells signal other parts of the immune system to confront the invader. These T-cells use a complex process to recognize the foreign pathogens and diseased cells. In a paper published this week in the journal Cell, researchers add a new level of understanding ...

Researchers identify transcription factors distinguishing glioblastoma stem cells

2014-04-10
The activity of four transcription factors – proteins that regulate the expression of other genes – appears to distinguish the small proportion of glioblastoma cells responsible for the aggressiveness and treatment resistance of the deadly brain tumor. The findings by a team of Massachusetts General Hospital (MGH) investigators, which will be published in the April 24 issue of Cell and are receiving advance online release, support the importance of epigenetics – processes controlling whether or not genes are expressed – in cancer pathology and identify molecular circuits ...

Yale researchers search for earliest roots of psychiatric disorders

2014-04-10
Newborns whose mothers were exposed during pregnancy to any one of a variety of environmental stressors — such as trauma, illness, and alcohol or drug abuse — become susceptible to various psychiatric disorders that frequently arise later in life. However, it has been unclear how these stressors affect the cells of the developing brain prenatally and give rise to conditions such as schizophrenia, post-traumatic stress disorder, and some forms of autism and bipolar disorders. Now, Yale University researchers have identified a single molecular mechanism in the developing ...

Some birds come first -- a new approach to species conservation

2014-04-10
New Haven, Conn.— A Yale-led research team has developed a new approach to species conservation that prioritizes genetic and geographic rarity and applied it to all 9,993 known bird species. "To date, conservation has emphasized the number of species, treating all species as equal," said Walter Jetz, the Yale evolutionary biologist who is lead author of a paper published April 10 in Current Biology. "But not all species are equal in their genetic or geographic rarity. We provide a framework for how such species information could be used for prioritizing conservation." Worldwide, ...

Penn study finds mechanism that regulates lung function in disease Birt-Hogg-Dube syndrome

2014-04-10
(PHILADELPHIA) – Researchers at Penn Medicine have discovered that the tumor suppressor gene folliculin (FLCN) is essential to normal lung function in patients with the rare disease Birt-Hogg-Dube (BHD) syndrome, a genetic disorder that affects the lungs, skin and kidneys. Folliculin's absence or mutated state has a cascading effect that leads to deteriorated lung integrity and an impairment of lung function, as reported in their findings in the current issue of Cell Reports. "We discovered that without normal FLCN the alveolar epithelial cells (AEC) in these patients' ...

Ancient 'spider' images reveal eye-opening secrets

Ancient spider images reveal eye-opening secrets
2014-04-10
VIDEO: This is a video showing the 305-million-year-old harvestman fossil. Click here for more information. Stunning images of a 305-million-year-old harvestman fossil reveal ancestors of the modern-day arachnids had two sets of eyes rather than one. The researchers say their findings, published in the journal Current Biology, add significant detail to the evolutionary story of this diverse and highly successful group of arthropods, which are found on every continent except Antarctica. University ...

Poor mimics can succeed as long as they mimic the right trait

2014-04-10
There are both perfect and imperfect mimics in nature. An imperfect mimic might have a different body shape, size or colour pattern arrangement compared to the species it mimics. Researchers have long been puzzled by the way poor mimicry can still be effective in fooling predators not to attack. In the journal Current Biology, researchers from Stockholm University now present a novel solution to the question of imperfect mimicry. Mimicry is when animals have the appearance of another species in order to avoid being attacked. For instance, hoverflies have a similar ...

LAST 30 PRESS RELEASES:

Psoriasis-linked gene mutation also impacts gut health

Widely-used technique for assessing IVF embryos may be flawed, study suggests

Alzheimer’s disrupts circadian rhythms of plaque-clearing brain cells

Nanoparticle blueprints reveal path to smarter medicines

Researchers get wind of hydrogen’s role in the gut

Supersolid spins into synchrony

New gene-editing tech holds promise for treating complex genetic diseases

Plastic pollution could linger at ocean surfaces for over a century, new research finds

TU Graz conducts research into endangered cultural heritage in the Western Himalayas

AI can be trained to provide safe advice for treating opioid use disorder in pregnancy: New study

A platform of gold reveals the forces of nature’s invisible glue

Drug which stops tumors' blood supply could help kids with bone cancer live longer

Disrupted sleep in teens identified as suicide risk factor

Traffic noise joins land clearance as damaging to bird survival

Innovative online monitoring system for farmland non-point source pollution enables automated monitoring of continuous cropping farmland

Stabilized fertilizers improve nitrogen use efficiency and reduce greenhouse gas emissions

Endangered Kangaroo Island ground dweller found in trees

Guardians of the coast: Philippine scientists unlock the climate power of mangroves in Eastern Visayas

Nano-biochar helps rice roots turn silver ions into less toxic nanoparticles

New ‘liquid metal’ composite material enables recyclable, flexible and reconfigurable electronics

Extinction rates have slowed across many plant and animal groups, study shows

Tiny fossil bone helps unlock history of the bowerbird

AI tool beats humans at detecting parasites in stool samples, Utah study finds

Innovative biochar research to boost circular economy: Join live talk by Prof. Salah Jellali on October 29

Early life sugar restriction linked to lasting heart benefits in adulthood

The Lancet: Study confirms cardiovascular benefits of semaglutide beyond weight loss

‘Weight loss’ drug helps heart regardless of amount of weight lost

First truly global picture of wide inequalities in care for women’s cancers

International Consortium of Women’s Mental Health Experts present scientific evidence to support classification of postpartum psychosis as a distinct disease

PET imaging of inflammation predicts recovery, guides therapy after heart attack

[Press-News.org] Team solves decades-old mystery of how cells keep from bursting
The findings may lead to new insights into immune deficiency, stroke and diabetes