How are necrotic cells recognized by their predators?
How are necrotic cells recognized by their predators?
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坏死细胞如何被捕食者识别？
DOI：
10.1080/21624054.2015.1120400
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Zhou,Zheng
中科院分区：
文献类型：
--
作者：
Li,Zao;Zhou,Zheng
坏死是一种细胞死亡类型，通常由细胞损伤引起，与人类疾病有关，包括神经元退化、中风和癌症。正在发生坏死的细胞被吞噬它们的捕食者细胞吞噬和降解。坏死细胞被识别和移除的机制仍然难以捉摸。在这里，我们评论我们最近的发现，揭示了坏死细胞识别的新的分子机制。通过对C.在优雅的神经元经历兴奋性毒性坏死的过程中，我们发现了一对受体/配体对，它使吞噬细胞能够识别坏死的神经元。吞噬细胞受体CED-1通过与其配体磷脂酰丝氨酸(PS)相互作用而激活，暴露在坏死细胞表面。此外，与人们普遍认为的坏死性细胞质膜破裂相反，我们发现坏死性C。优雅神经元在维持质膜完整性的同时，活跃地在其外表面呈现PS。我们进一步确定了两种控制PS呈现的机制，其中一种与正在经历细胞凋亡的细胞共享，这是一种“细胞自杀”事件，而另一种是坏死神经元所独有的。钙离子的内流是一种关键的坏死触发因子，它参与激活神经元PS-扰乱酶以应对PS暴露。我们认为，通过吞噬细胞来控制PS暴露和坏死细胞识别的机制可能从蠕虫到人类都是保守的。
Necrosis is a type of cell death often caused by cell injury and is linked to human diseases including neuron degeneration, stroke, and cancer. Cells undergoing necrosis are engulfed and degraded by engulfing cells, their predators. The mechanisms by which necrotic cells are recognized and removed remain elusive. Here we comment on our recent findings that reveal new molecular mechanisms of necrotic-cell recognition. Through studying theC. eleganstouch neurons undergoing excitotoxic necrosis, we identified a receptor/ligand pair that enables engulfing cells to recognize necrotic neurons. The phagocytic receptor CED-1 is activated through interaction with its ligand phosphatidylserine (PS), exposed on the surface of necrotic cells. Furthermore, against the common belief that necrotic cells have ruptured plasma membrane, we found that necroticC. eleganstouch neurons actively present PS on their outer surfaces while maintaining plasma membrane integrity. We further identified 2 mechanisms governing the presentation of PS, one of which is shared with cells undergoing apoptosis, a “cell suicide” event, whereas the other is unique to necrotic neurons. The influx of Ca2+, a key necrosis-triggering factor, is implicated in activating a neuronal PS-scramblase for PS exposure. We propose that the mechanisms controlling PS-exposure and necrotic-cell recognition by engulfing cells are likely conserved from worms to humans.