Researchers from Kyushu University in Japan have made a groundbreaking discovery about the calcium-based mechanism that plays a crucial role in the removal of dead cells, shedding light on how our bodies protect themselves from injury and disease. This study provides valuable insights into understanding various epithelial barrier disruption-related diseases and may contribute to the development of new preventive measures and treatments for chronic inflammation.
Calcium’s Crucial Role in Epithelial Cell Disposal
The research team, led by Professor Junichi Ikenouchi, has uncovered a fascinating mechanism by which calcium ions play a vital role in the efficient removal of dying or apoptotic cells from epithelial tissues. The surfaces of our bodies, including the skin and internal organs, are covered by sheets of epithelial cells that act as vital barriers.
When these cells become damaged and die, neighboring cells quickly work together to push them out and seal any gaps, preventing the entry of foreign substances that could lead to infections or inflammation. This complex process is essential for maintaining a healthy epithelial barrier, but the exact mechanism behind it has remained a mystery until now.
Visualizing the Calcium Response in Epithelial Cell Extrusion
The researchers used a focused laser to induce apoptosis in individual epithelial cells and observed the response in the surrounding cells. By modifying the cells to express special calcium ion probes called GCaMP6, they were able to visualize real-time calcium changes. Interestingly, they found that the neighbors of the apoptotic cell showed a significant spike in calcium levels, particularly near the membrane regions interfacing with the dying cell. This phenomenon was aptly named the “calcium response in effectors of apical extrusion (CaRE).”
Further investigation revealed that the activation of IP3 receptors, proteins that help regulate calcium ion levels, is essential for the expulsion of apoptotic cells. A specific subset of IP3 receptors, particularly those located near desmosomes, was found to play a key role in the CaRE mechanism.
The Crucial Role of Desmosomes in Epithelial Tissue Integrity
Desmosomes are cell adhesion structures that form strong connections between cells, acting like buttons that hold them together. They are especially important in tissues like skin and organ linings, helping to keep everything intact and functioning properly. The research team found that the activation of IP3 receptors near desmosomes is necessary for triggering the contraction of a group of proteins known as the actomyosin complex, which helps cells change shape and move, facilitating the removal of apoptotic cells.
This study has shed light on a newfound role of IP3 receptors in desmosomes, which were previously thought to be involved only in mechanical connections between epithelial cells. The researchers note that further analysis is needed to determine whether the CaRE mechanism also functions in living organisms, whether it varies between different organ tissues, and whether other factors also play a role.
