Scientists have found that extracellular calcium mediates the activation of a membrane protein that waves the flag signaling cell death.
A research team co-led by scientists from Kyoto University Institute for Integrated Cell-Material Sciences (iCeMS) in Japan has uncovered mechanisms of how dying cells activate a protein that triggers an ‘eat me’ signal for immune cells to clean up the debris. The findings were recently published in the journal
Activation Process of Xkr4
Researchers had previously discovered that, to act as a scramblase for phosphatidylserine, The C-terminal cytoplasmic tail of Xkr4 first has to be cleaved, forming a dimer with another Xkr4 and exposing a binding site. This binding site then connects to another protein fragment called XRCC4.
However, the binding of XRCC4 to Xkr4 alone is not enough to activate Xkr4 in the experimental setting. This suggested that another ingredient was required.
The Role of Calcium Ions
The research team in Japan discovered that calcium ions are required to enable activation of Xkr4. The positively charged calcium ions outside the cellular environment bind to three negatively charged DOI: 10.1038/s41467-023-40934-2