Stocktaking

Calcium is one of the most important minerals in the human body, and its level in the body's cells is under tight control. The cell needs calcium ions for many essential processes, including, among others, cell growth, transmission of nerve signals, muscle contraction, bone formation, and the fertilization process.

Calcium is one of the most important minerals in the human body, and its level in the body's cells is under tight control. The cell needs calcium ions for many essential processes, including, among others, cell growth, transmission of nerve signals, muscle contraction, bone formation, and the fertilization process. Therefore, it is essential that a low but constant concentration of calcium ions is always maintained inside the cells. Changes in calcium concentrations - as it is becoming clear - may lead to disturbances in cell function, and cause various diseases. Thus, for example, too high a concentration of calcium ions in nerve cells causes their death, which may cause neurodegenerative diseases. In addition, scientists believe that an imbalance in calcium levels is associated with various types of cancer and cardiovascular diseases. Prof. Eitan Reuvani, from the department of biological chemistry at the institute, recently discovered the role of a new protein, which is involved in the process of controlling and balancing the calcium level in the cell.

To make sure that there is a sufficient and available supply of calcium ions in the cell, and to prevent uncontrolled "jumps" in its concentration in the cell, the calcium is stored in cellular stores - a kind of membrane-encased bubbles. These warehouses know how to replenish the stock kept in them as soon as it starts to run low. But how does the cell know exactly how much calcium to order? To date, scientists have known two molecules that participate in controlling the process of calcium entering the cell and storing it in stores. One molecule, STIM, performs an "inventory count" in the warehouses, and detects a decrease in the amount of calcium. In that case it reports to the second molecule - Orai. This molecule is actually a selective protein channel for calcium ions, located on the cell membrane. Following the signaling of the STIM molecule, the channel opens, calcium ions flow into the cell, and are stored in stores. However, another key element is missing from the picture: what is the factor that controls the closing of the canals, thus preventing the warehouses from overflowing, and spilling their contents out? Prof. Reuvani, together with his group members Raz Pelti, Adi Reva, Ido Kaminsky and Ruth Meler, identified a new protein that helps control the calcium storage mechanism - a discovery recently published in the scientific journal Cell. It appears that when the Orai channels open, the new protein, called SARAF, gradually inhibits the activity of STIM, thus causing the channels to close in a controlled manner.

When the scientists caused the activity of the inhibitory protein to stop, using methods of genetic engineering, excess calcium accumulated in the cell, causing disruptions in various processes in the cell. Another diagnosis of the researchers was that the inhibitory protein, SARAF, moves together with STIM to the cell membrane (where the channels are located) - which provides further evidence that this protein is indeed involved in the inhibition of STIM.

Cells expressing the SARAF protein (stained with a red fluorescent marker), and cells expressing STIM1 (stained with a green fluorescent marker). The right picture, in which the two proteins are visible, shows that they are found together

Although there is no direct evidence of a link between SARAF mutations and diseases in humans, recent studies have identified the SARAF protein as a biomarker involved in diseases such as prostate cancer, Alzheimer's, and heart muscle dysfunction - all diseases characterized by abnormal levels of calcium in the cells.

Prof. Reuveni: "The SARAF protein is produced in all body cells, but its level is particularly high in the cells of the immune system and brain cells. We still don't know exactly what he does there and how he works, and these are our tasks for further research."

SARAF protein is labeled with green fluorescent protein. The color intensifies as the protein approaches the cell membrane