illustration by Leif Parsons

A SWELL Discovery

By its nature, a cell’s membrane is permeable to water. So if water levels in the cell’s environment increase, the cell will swell. If it can’t pump out the excess water, the cell will burst. But most cells don’t burst, and HHMI Investigator Ardem Patapoutian of the Scripps Research Institute has identified a gene that helps explain why.

Because water tends to follow solutes—the ions and other chemicals dissolved in water—a cell can manage its water content by managing its solutes. In the 1980s, scientists discovered that a cellular ion channel—called volume-regulated anion channel (VRAC)—opens in response to swelling to allow the outflow of negatively charged ions, which take excess water with them.

“Although scientists have known about the activity of VRAC for almost 30 years, its molecular identity has remained a mystery,” says Patapoutian. To find the VRAC genes, his team created fluorescent cells whose glow was muted when VRAC channels opened. The researchers inactivated more than 20,000 genes, one by one, and watched the effect on the glowing cells. Silencing of only one allowed the glow to continue, implying that VRAC had been inactivated. They named that gene SWELL1 and published their findings on April 10, 2014, in the journal Cell.

“When cells swell, the SWELL1 protein is activated and pumps chloride and other solutes out of the cell, which initiates the process to shrink a cell back to original volume,” says Patapoutian.

Now that the team has a molecular understanding of VRAC, they plan to investigate how the channel senses volume change and the role SWELL1 plays in physiology and disease.