The cut pieces of XRCC4 protein travel out of the nucleus to the cell membrane to activate scramblases and activate an “eat-me” signal recognized by phagocytes.

Scientists have discovered molecular mechanisms involved in eliminating unwanted cells. A nuclear protein fragment released into the cytoplasm activates a membrane protein to display a lipid on the cell surface, signaling other cells to get rid of it.

Every day, ten billion cells die and are flooded by phagocytes. If this was not the case, the dead cells would erupt causing an autoimmune reaction, so the dead cells are eliminated as part of the body’s maintenance, displaying an “eat me” signal on their phagocyte-recognized surface.

During this process, lipids are inverted between the inside and outside of the cell membrane through a variety of proteins called scramblases {enzymes responsible for moving phospholipids between the two layers of the cell membrane}. A nuclear protein fragment has been found to activate Xkr4  (reconstitution protei) to display the “eat me” signal in phagocytes. In particular, scientists have found that cell death signals lead to a part of it leaves the nucleus, activating Xkr4, which eventually transports lipids to the cell surface to alert phagocytes.

Xkr4 is just one of the remodeling proteins. Others are activated much faster during cell death. Since the Xkr4 pathway is strongly expressed in the brain, it is probably important for brain function.