Spectrin as a marker for dead cells

In human body, billions of cells are renewed every day and the dead cells need to be removed promptly to prevent various diseases. Phagocytes such as macrophages and dendritic cells in the immune system are playing important roles in cleaning dead cell by recognizing specific markers exposed on dead cells.

 

Over the past decades, scientists have found that phosphatidylserine on cell membrane can act as a dead cell marker for apoptotic cells. However, recent evidence shows that other cellular components can also behave as dead cell markers mediating dead cell recognition by the immune system, suggesting that dead cell clearance is more complex than previously thought.

 

Recently, scientists from the Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences found that SCARA1 (or CD204), a scavenger receptor highly expressed on macrophages, can recognizes dead cells specifically via spectrin in the presence of Ca2+. Besides, they found that the interaction between SCARA1 and spectrin occurs between the C-terminal domain of SCARA1 and the SPEC repeats of spectrin and the divalent cation such as Ca2+ is required for the interaction.

 

Spectrin is expressed in almost all eukaryotic cells as a cytoskeleton component locating beneath the cytoplasmic side of cell membrane. It was initially identified in red blood cells and known as “ghost proteins”. This study suggested that spectrin can also function as a marker for dead cells and mediate the immune recognition of dead cells, and showed that macrophages can internalize dead cells or debris from both red blood cells and other cells through the interaction between CD204 and spectrin.

 

Furthermore, as dead cell clearance is critical for maintaining body homeostasis, this study, along with previous finding, suggested that intracellular components could play important roles in dead cell removal. Clarifying the mechanisms of these pathways would facilitate the therapeutic strategies against the related diseases in the future.

 

This study was published in Journal of Biological Chemistry. It is supported by the grants from Chinese Academy of Sciences and the National Natural Science Foundation of China.

 

Reference：http://www.jbc.org/content/early/2019/10/25/jbc.RA119.010110.long