Necrotic Cells Actively Attract Phagocytes through the Collaborative Action of Two Distinct PS-Exposure Mechanisms

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Necrosis is a type of cell death often caused by cell injury and is linked to human diseases including neuron degeneration, stroke, and cancer. Necrotic cells undergo distinct morphological changes, including swelling, before being engulfed and degraded by engulfing cells. The clearance of necrotic cells from animal bodies is important for wound healing and for preventing harmful inflammatory and autoimmune responses. However, the mechanisms by which necrotic cells are removed remain elusive. We study the recognition of necrotic neurons in the nematode C. elegans. There is a common belief that the plasma membrane of necrotic cells are ruptured, allowing the detection of phosphatidylserine (PS), a so-called “eat me” signal molecule, by specific transmembrane receptors on the surface of engulfing cells. Contrary to this belief, we found that necrotic neurons actively present PS to their outer surface through two parallel molecular mechanisms, one of which is shared by cells undergoing apoptosis, a “cell suicide” event, whereas the other is unique to necrotic cells. Ca2+-influx, a key factor that triggers necrosis, is implicated in activating a unique PS-scramblase. Our findings reveal novel necrotic cell-specific “eat me” signal-exposure mechanisms and indicate that cells that die through different mechanisms (necrosis and apoptosis) utilize both common and unique mechanisms to attract engulfing cells. They further demonstrate that C. elegans is an effective model system for studying the fate of necrotic cells.

Vyšlo v časopise: Necrotic Cells Actively Attract Phagocytes through the Collaborative Action of Two Distinct PS-Exposure Mechanisms. PLoS Genet 11(6): e32767. doi:10.1371/journal.pgen.1005285
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005285

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