The researchers have revealed for the first time how white blood cells control the final moments of their death, helping their own removal from the human body. They have identified a protein called Plexin B2 within dying cells that is responsible for coordinating a key stage of apoptosis (cell death).
Published in Cell Reports, the study is a significant step forward in understanding what may trigger numerous disease states such as inflammation and autoimmunity.
Lead researcher said the key function of Plexin B2 was discovered when they used CRISPR gene-editing technology to delete the protein from white blood cells. The authors find that the protein plexin B2 (PlexB2), a transmembrane receptor that regulates axonal guidance in neurons, is enriched in the ApoBDs of THP1 monocytes and is a caspase 3/7 substrate.
"Normally, dying white blood cells undergo a dynamic death and shoot out long, beaded, necklace-like structures and fragment into small pieces," the author said. "However, since our discovery of this process in 2015, we have not understood how or why this dance of death occurs.
"Our new research identified the protein Plexin B2 as the first molecule which controls this event."The author said genetically deleting Plexin B2 prevented dying cells from forming beaded structures. "Surprisingly, this defect in the cell death process significantly compromised their removal by the garbage trucks of the body, known as phagocytes," the author said.
"Typically, dying cells send 'find me' and 'eat me' signals to phagocytes, however, deletion of Plexin B2 could limit the number of fragments that are 'ready-to-eat'."
This study follows research - published in June 2019 in Cell Death and Differentiation - from the author, which also demonstrated the importance of dying cell fragmentation, through a process called blebbing, to aid in the efficient removal of cells by phagocytes.
"Excitingly, the next phase of our research is to take our key basic biology discoveries and examine them in pre-clinical models of autoimmunity," the author said.
Regulator of apoptotic cell death identified!
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