Scripps Research Institute scientists have solved the puzzle of a cell biology three decades, they identified a transmembrane protein called SWELL1, which is located on the cell membrane, specific mutations alter the properties of the protein VRAC channel .
All cells have one of the most basic functions, namely to control their volume to avoid excessive expansion. For decades, people have been looking for to achieve this function protein, now Scripps Research Institute (TSRI) scientists have finally found it.
This protein is called SWELL1 solve an important puzzle cell biology, and health and disease are closely related. For example, the abnormal protein function, can cause a severe immune deficiency.
“Understanding this protein and its encoding gene, as people opened a new research direction,” professor who led the research Ardem Patapoutian said. The study published as the cover article in the April 10 issue of Cell.
The vast majority of water molecules can easily pass through the cell membrane, and the flow of water molecules tend to equilibrium solute concentration inside and outside the membrane. “Water is actually to go along with the solute,” first author Zhaozhu Qiu said. “Extracellular solute concentration decrease or increase of intracellular solute concentration, the cell will be filled with water.”
A few decades ago people found through experiments, there is a certain ion channels on the cell membrane, a key safety valve can be used as cell expansion, they will this unknown ion channel called VRAC (volume regulated anion channel). When cells are expanded VRAC opens, allowing chloride ions and other negatively charged molecules flow. Then will follow the outflow of water molecules, thereby reducing the expansion of the cells.
“Over the past three decades, scientists have been aware of the existence VRAC channels, but it does not understand,” Patapoutian said.
Due to technical limitations, it has not been possible to find the composition of the protein and its gene VRAC. Now, Qiu and his colleagues conducted a rapid high-throughput fluorescence screening in the new study. They transform human cells to produce a special fluorescent protein when cells swell VRAC channels open, the light emitted by this protein will be quenched.
Help Novartis Research Foundation Genomics Research Institute (Genomics Institute of the Novartis Research Foundation) automated screening experts, researchers trained a large number of cells for screening and blocking different genes by RNA interference in these cells, respectively, activity. They are mainly looking for sustained light-emitting cells, continuous light indicates that gene inactivation destroys the cells of VRAC.
After several rounds of testing research team eventually found a gene. 2003 scientists have discovered the gene, and called LRRC8, but when people only know that it may encode a transmembrane protein. Now, researchers will rename it to SWELL1.
The researchers found that by further experiments, SWELL1 indeed located on the cell membrane, and specific mutations alter the properties of the protein VRAC channel. “It is at least a major part VRAC channels, is a cell biologist at the long-term pursuit of proteins,” Patapoutian said.
Next, the research team will further study SWELL1 function. For example, in a mouse model was observed lack of influence caused SWELL1 different cell types.
It was originally discovered in 2003 that the gene, because this gene mutation causes a very rare non agammaglobulinemia (agammaglobulinemia). Patients with this disease lack of antibody-producing B cells, making it vulnerable to infection. This also explains, SWELL1 normal development of B cells is required for protein.
“Previous research has pointed out, because a stroke can cause brain swelling, so this volume-sensitive ion channels associated with stroke. Additionally, this protein may also be involved in the insulin-secreting pancreatic cells.” Patapoutian said. “This leads us one to be resolved.”