A research team from Kyushu University in Japan has recently discovered a calcium-based mechanism that plays a key role in the disposal of dead cells, shedding light on how our bodies protect themselves from injury and disease. In their study, published in Current Biology on September 23, 2024, the team unveiled how calcium ion levels are essential for the efficient removal of dying or apoptotic cells from epithelial tissues (cells lining the body surface), using genetically engineered epithelial tissue cultures, molecular markers, and advanced imaging techniques.

 

To begin with, the team induced apoptosis in individual epithelial cells using a focused laser and observed the response in the surrounding cells. They then observed how nearby cells reacted by modifying them to express special calcium ion probes called GCaMP6, which allowed them 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. The researchers named this intriguing phenomenon the "calcium response in effectors of apical extrusion (CaRE)." Delving deeper into this newly discovered mechanism, the team next examined the role of IP3 receptors, proteins present inside cells that help regulate calcium ion levels. They found that inhibiting the activity of IP3 receptors or removing their associated genes completely prevented the expulsion of apoptotic cells. Desmosomes are cell adhesion structures that form strong connections between cells, acting like buttons that hold them together. The team found that the activation of IP3 receptors near desmosomes is necessary for triggering the contraction of a group of proteins known as actomyosin complex, which helps cells change shape and move, facilitating the removal of apoptotic cells.

 

As this study was conducted on cultured cells, the team notes that further analysis of the CaRE mechanism are needed to determine whether the mechanism also function in living organisms, if it varies between different organ tissues, and whether other factors also play a role. Overall, this study advances our understanding of how our bodies maintain a healthy epithelium -- something many of us take for granted.