Scientists at the Institute of Integrated Cell Materials Sciences (iCeMS) and colleagues in Japan have unveiled molecular mechanisms involved in the elimination of unwanted cells in the body.
A nuclear protein fragment released into the cytoplasm activates a plasma membrane protein to display lipid on the surface of the cells, signaling other cells to get rid of it. The findings were published in the journal Cell molecular.
“Every day, ten billion cells die and are surrounded by blood cells called phagocytes. If this did not happen, dead cells would explode, triggering an autoimmune reaction,” bio- iCeMS expert Jun Suzuki, who led the study. “It’s important to understand how dead cells are removed as part of maintaining our body.”
Scientists already know that dead cells display an ‘eat me’ mark on their surface that is recognized by phagocytes. Through this process, lipids are transferred between the inner and outer parts of the cell membrane through various proteins called scramblases.
Suzuki and his team have already identified several of these lipid-secreting proteins, but some of their activation mechanisms have been unclear.
To solve this, the team used several screening methods to study the abrasive protein called Xkr4. The overarching goal was to extract the genes that are active at the time of cell death and migrate specifically to Xkr4 and its associated proteins to understand how they interact. .
“We found that a nuclear protein chip activates Xkr4 to display the‘ I ate ’signal to phagocytes,” says iCeMS cell biologist Masahiro Maruoka, the first author of the study.
In particular, the scientists found that signs of cell death lead to a nuclear protein, called XRCC4, undergoing enzyme cleavage.
A fragment of XRCC4 leaves the nucleus, activating Xkr4, which forms a dimer: binding identical pieces in alignment. Both XRCC4 binding and dimer formation are essential for Xkr4 to move lipids on the cell surface to alert phagocytes.
Xkr4 is just one of the abrasive proteins. Others are activated much more rapidly during cell death. The team now wants to understand when and why the Xkr4 path is specifically activated. Because it is strongly expressed in the brain, it appears to be important for brain function.
We are now studying the elimination of unwanted cells or areas in the brain to better understand this process. “
iCeMS cell biologist Masahiro Maruoka, First Author and Study Cell biologist, Institute for Integrated Cell Material Sciences (iCeMS)
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Magazine Reference:
Maruoka, M., et al. (2021) Caspase activation releases a nuclear protein fragment that stimulates phospholipid scavenging at the plasma membrane. Cell molecular. doi.org/10.1016/j.molcel.2021.02.025.