Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Datun Road, Chaoyang District, Beijing 100101, China.
Science. 2010 Mar 5;327(5970):1261-4. doi: 10.1126/science.1184840. Epub 2010 Feb 4.
The cell surface receptor CED-1 mediates apoptotic cell recognition by phagocytic cells, enabling cell corpse clearance in Caenorhabditis elegans. Here, we found that the C. elegans intracellular protein sorting complex, retromer, was required for cell corpse clearance by mediating the recycling of CED-1. Retromer was recruited to the surfaces of phagosomes containing cell corpses, and its loss of function caused defective cell corpse removal. The retromer probably acted through direct interaction with CED-1 in the cell corpse recognition pathway. In the absence of retromer function, CED-1 associated with lysosomes and failed to recycle from phagosomes and cytosol to the plasma membrane. Thus, retromer is an essential mediator of apoptotic cell clearance by regulating phagocytic receptor(s) during cell corpse engulfment.
细胞表面受体 CED-1 介导吞噬细胞对凋亡细胞的识别,从而促进秀丽隐杆线虫细胞尸清除。在这里,我们发现,秀丽隐杆线虫细胞内蛋白分选复合物 retromer 通过介导 CED-1 的循环,对细胞尸清除是必需的。retromer 被招募到含有细胞尸的吞噬体表面,其功能丧失导致细胞尸清除缺陷。retromer 可能通过在细胞尸识别途径中与 CED-1 直接相互作用而发挥作用。在没有 retromer 功能的情况下,CED-1 与溶酶体结合,无法从吞噬体和细胞质循环到质膜。因此,retromer 通过调节吞噬细胞受体在细胞尸吞噬过程中,是凋亡细胞清除的一个重要介质。