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程序性细胞死亡(细胞凋亡)是一个对生物体的发育、组织的动态稳定至关重要的生物学过程。细胞凋亡的发生过程如下:在决定要凋亡的细胞内,一些死亡基因被启动,细胞被杀死,这称为凋亡的执行过程。随后,凋亡细胞被吞噬细胞识别并内吞;最终,凋亡细胞在吞噬细胞内被完全降解。凋亡细胞的吞噬和降解是细胞凋亡程序的重要环节,凋亡细胞的清除障碍会引起炎症疾病和免疫紊乱。在秀丽隐杆线虫中,吞噬受体CED-1对于吞噬细胞识别凋亡细胞起着关键作用。本研究发现细胞内的蛋白分选复合体retromer可以通过调控CED-1在细胞膜与细胞质之间的循环来参与凋亡细胞的清除过程。Retromer会被招募到吞噬小体的表面,介导CED-1从吞噬小体到细胞膜的回收过程。当retromer丧失功能时,CED-1会被运送到溶酶体降解,CED-1的这种减少造成了凋亡细胞的清除障碍。我们的工作揭示了retromer复合体参与凋亡细胞清除的这一新功能,并发现了吞噬受体的一种新的调控机制。
Programmed cell death (apoptosis) is a biological process that is crucial for the development of the organism and the dynamic stabilization of the tissue. Apoptosis occurs as follows: In a cell that is determined to be apoptotic, some of the death genes are activated and the cells are killed, which is called the process of apoptosis. Subsequently, apoptotic cells are recognized and endocytosed by phagocytes; eventually, apoptotic cells are completely degraded within phagocytes. Phagocytosis and degradation of apoptotic cells are an important part of the apoptotic process, and clearance of apoptotic cells can cause inflammatory diseases and immune disorders. In Caenorhabditis elegans, the phagocytic receptor CED-1 plays a key role in phagocyte identification of apoptotic cells. This study found that intracellular protein sorting complex retromer can participate in the clearance process of apoptotic cells by regulating the circulation of CED-1 between the cell membrane and the cytoplasm. Retromer is recruited to the surface of the phagosome to mediate the recovery of CED-1 from the phagosome to the cell membrane. When retromer loses its function, CED-1 is transported to lysosomes for degradation, and this reduction in CED-1 results in the removal of apoptotic cells. Our work reveals that the retromer complex is involved in this new function of apoptotic cell clearance and has discovered a new regulatory mechanism of the phagocytic receptor.