Extracellular calcium enters a pocket in the transmembrane region of scramblase, triggering the scramblases activation. This exposes phosphatidylserine (PS) on the cell surface, functioning as a distinct marker for the removal of undesirable cells. Credit: Mindy Takamiya/Kyoto University iCeMS
Activation Process of Xkr4
Researchers had formerly discovered that, to act as a scramblase for phosphatidylserine, The C-terminal cytoplasmic tail of Xkr4 initially needs to be cleaved, forming a dimer with another Xkr4 and exposing a binding website. This binding website then connects to another protein piece called XRCC4.
The binding of XRCC4 to Xkr4 alone is not enough to activate Xkr4 in the speculative setting. This recommended that another ingredient was needed.
The Role of Calcium Ions
The research group in Japan discovered that calcium ions are needed to make it possible for activation of Xkr4. The positively charged calcium ions outside the cellular environment bind to three negatively charged amino acids on 2 helices on the Xkr4 protein. This binding changes Xkr4 into a full-activated state from an intermediate state.
” We found that extracellular calcium functions as a molecular glue for Xkr4s transmembrane helices, triggering it,” described iCeMS biochemist Jun Suzuki.
Calciums Unexpected Role and Future Research
Whats surprising is that extracellular calcium is known to be associated with controling the activity of proteins outside and inside the cellular environment, but not within the cell membrane itself. “Here, suddenly, we found that extracellular calcium is infiltrated into the transmembrane regions of proteins to link 2 transmembrane helices,” Suzuki said.
The study also suggests that calcium ions may be crucial for activation of other members of the Xkr protein family, particularly Xkr8 and Xkr9, which might help clarify the systems by which these and other scramblase proteins function.
The next step for the group is to take a look at the function of Xkr4 in afferent neuron and explore their role in the brain.
Referral: “Extracellular calcium functions as a molecular glue for transmembrane helices to activate the scramblase Xkr4” by Panpan Zhang, Masahiro Maruoka, Ryo Suzuki, Hikaru Katani, Yu Dou, Daniel M. Packwood, Hidetaka Kosako, Motomu Tanaka and Jun Suzuki, 11 September 2023, Nature Communications.DOI: 10.1038/ s41467-023-40934-2.
This exposes phosphatidylserine (PS) on the cell surface area, serving as a distinct marker for the removal of unwanted cells. The favorably charged calcium ions outside the cellular environment bind to 3 negatively charged amino acids on 2 helices on the Xkr4 protein.
Japanese researchers discovered how a protein, Xkr4, is activated by calcium ions to signal immune cells for tidying up dying cells. This finding, showing calciums unique function in the cell membrane, could supply brand-new insights into cellular cleanup systems.
Scientists have actually discovered that extracellular calcium mediates the activation of a membrane protein that waves the flag signaling cell death.
A research study group co-led by researchers from Kyoto University Institute for Integrated Cell-Material Sciences (iCeMS) in Japan has discovered mechanisms of how passing away cells activate a protein that activates an eat me signal for immune cells to clean up the debris. The findings were just recently published in the journal Nature Communications.
Function of Xkr4 Protein in Cell Death
The protein is called Xkr4, one of the Xkr family of proteins found in cell membranes. Xkr4 scrambles the phospholipid phosphatidylserine from the inner part of the cell membrane, where it usually lives, to its outside. Phosphatidylserines moving to the outer part of the membrane is the signal that the cell is passing away, and which attracts debris-gobbling phagocytes.
The protein is called Xkr4, one of the Xkr family of proteins found in cell membranes. Xkr4 scrambles the phospholipid phosphatidylserine from the inner part of the cell membrane, where it typically resides, to its outside. Phosphatidylserines relocation to the outer part of the membrane is the signal that the cell is dying, and which brings in debris-gobbling phagocytes.