A “swell” discovery on how cells keep in shape

An important finding published in the journal Cell adds insight to a 30-year mystery about how cells sense their environment, and could translate into help for diseases where water balance and cell volume are key, such as diabetes and stroke.

Our cells are constantly in a state of flux, working to maintain equilibrium to keep them alive. For instance, their membranes are permeable to water, which means that as water levels in their local environment change, so too does their internal concentration of ions, such as chloride, potassium, and sodium. Ion channels embedded in the membrane must pay close attention to their environment to determine when to open and close to maintain balance.

In the case of one type of ion channel called the volume-regulated anion channel, or VRAC, the important factor is cell swelling. When a cell’s environment is challenged with more water, for example, it begins to swell until, at some point before it bursts, it simply stops. It does so because, as the cell expands, VRAC pores open up and allow negatively charged ions to pass through the cell membrane.

The protein was first shown to exist in the 1980s, but the details of its function and its molecular identity have remained an enigma. So when ZhaoZhu Qiu joined Ardem Patapoutian's lab as a postdoctoral fellow at the Genomics Institute of the Novartis Research Foundation (GNF) looking for a good challenge, VRAC seemed like the perfect candidate. The Patapoutian lab is interested in the general question of how mechanical forces translate into biochemical signals, and GNF’s expertise in technology and high-throughput screens was critical in enabling this explorative project. Qiu spent the next four years working to uncover the molecular identity of VRAC.

"It is a fundamental biological process that has been studied for many years without any molecular insights. The identification of Swell1 I think will enable in-depth understanding of this basic cellular process" said Qiu.

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