A team of Japanese researchers has unveiled the process by which calcium ions activate a protein, Xkr4, prompting immune cells to clear out dying cells. This breakthrough highlights the unique involvement of calcium in the cell membrane and could lead to deeper understanding of cellular cleaning processes.
The role of external calcium in triggering a membrane protein, signaling the occurrence of cell death, has been identified.
Kyoto University’s Institute for Integrated Cell-Material Sciences (iCeMS) researchers in Japan have elucidated how a protein becomes activated in dying cells, signaling immune cells to remove cellular debris. These discoveries were published in Nature Communications.
Understanding Xkr4 Protein’s Function in Cell Demise
Xkr4 is a member of the Xkr protein family present in cell membranes. It repositions the phospholipid phosphatidylserine from the cell membrane’s inner to outer part. This movement indicates cell death and attracts phagocytes to consume the debris.
Extracellular calcium enters a specific region of the scramblase protein, initiating its activation. This reveals phosphatidylserine (PS) on the cell surface, marking cells for removal. Credit goes to Mindy Takamiya at Kyoto University’s iCeMS for this insight.
How Xkr4 Gets Activated
Previous research showed that for Xkr4 to function as a scramblase for phosphatidylserine, its C-terminal cytoplasmic tail must be severed, creating a dimer with another Xkr4 and revealing a binding site. This site then attaches to another protein, XRCC4.
Yet, XRCC4’s binding to Xkr4 alone doesn’t fully activate Xkr4, hinting at the need for another component.
The Critical Role of Calcium Ions
The research team discovered the necessity of calcium ions for Xkr4 activation. Positively charged calcium ions outside the cell bind to three negatively charged amino acids on two helices of the Xkr4 protein. This interaction transitions Xkr4 to a fully activated state from an intermediate state.
Jun Suzuki, a biochemist at iCeMS, noted, “Extracellular calcium acts as a molecular adhesive for Xkr4’s transmembrane helices, activating it.”
The Surprising Function of Calcium and Future Investigations
It’s known that extracellular calcium influences protein activities both outside and inside cells, but its role within the cell membrane was unanticipated. Suzuki remarked, “We found that extracellular calcium unexpectedly permeates into transmembrane regions of proteins, connecting two transmembrane helices.”
The study also suggests that calcium ions may be crucial for activating other Xkr protein family members, like Xkr8 and Xkr9. This could shed light on how these scramblase proteins operate.
The research team plans to study Xkr4’s role in nerve cells and its function in the brain.
Source: “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
Table of Contents
Frequently Asked Questions (FAQs) about Calcium’s role in cell death
What is the main discovery of the Japanese scientists regarding calcium?
The Japanese researchers discovered that calcium ions activate the protein Xkr4, which signals immune cells to clear dying cells, highlighting calcium’s unique role in the cell membrane.
How does the Xkr4 protein function in cell death?
Xkr4, part of the Xkr protein family, moves phosphatidylserine from the inner to the outer part of the cell membrane. This relocation signals that the cell is dying and attracts phagocytes to consume the cellular debris.
What role does extracellular calcium play in activating the Xkr4 protein?
Extracellular calcium binds to specific regions on the Xkr4 protein, transitioning it from an intermediate to a fully activated state. This binding is crucial for the protein’s activation and function.
What are the implications of this study for future research?
This study suggests that calcium ions might be important in activating other Xkr protein family members and could clarify the mechanisms of scramblase proteins. It also opens avenues for exploring the function of Xkr4 in nerve cells and the brain.
More about Calcium’s role in cell death
- Kyoto University Institute for Integrated Cell-Material Sciences
- Nature Communications Journal
- Study on Xkr4 Protein Activation
- Role of Calcium Ions in Cellular Processes
- Research on Cell Death Mechanisms
4 comments
interesting article, but could’ve used more details on how this affects our daily health. still, good to see progress in cellular biology!
I wonder if this research has any implications for treating diseases? it’s amazing how tiny things like calcium ions can have such big impacts.
A bit technical for my taste, but it’s fascinating how much we’re still learning about the human body. great job to the researchers_xD83D__xDC4D_
wow, this is really cool stuff! never knew calcium had such an important role in cell death, science is always surprising us_xD83D__xDE0A_