trim-21 promotes proteasomal degradation of CED-1 for apoptotic cell clearance in C. elegans.
trim-21 promotes proteasomal degradation of CED-1 for apoptotic cell clearance in C. elegans.
复制标题
trim-21 促进 CED-1 的蛋白酶体降解，从而清除秀丽隐杆线虫中的凋亡细胞。
DOI：
10.7554/elife.76436
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发表时间：
2022-08-05
期刊：
影响因子：
7.7
通讯作者：
Xiao, Hui
中科院分区：
文献类型：
--
作者：
Yuan, Lei;Li, Peiyao;Jing, Huiru;Zheng, Qian;Xiao, Hui
吞噬细胞受体CED-1介导吞噬细胞识别凋亡细胞，使秀丽隐杆线虫中的细胞尸体清除成为可能。是否维持适当水平的CED-1以执行吞噬功能仍然未知。在这里，我们确定了C。E3泛素连接酶三联基序包含-21（TRIM-21）作为CED-1途径的一个组成部分，用于凋亡细胞清除。当CED-1的NPXY基序与衔接蛋白CED-6结合或CED-1的YXXL基序被酪氨酸激酶SRC-1磷酸化并随后与含有SH 2结构域的衔接蛋白NCK-1结合时，TRIM-21与UBC-21一起发挥作用，催化CED-1上的K48连接的多聚泛素化，靶向其进行蛋白酶体降解。在不存在TRIM-21的情况下，CED-1在诱导后积累并驱动细胞尸体降解缺陷，如通过与VHA-10的直接结合所证明的。这些发现揭示了维持适当水平的CED-1以调节凋亡细胞清除的独特机制。
The phagocytic receptor CED-1 mediates apoptotic cell recognition by phagocytic cells, enabling cell corpse clearance in Caenorhabditis elegans. Whether appropriate levels of CED-1 are maintained for executing the engulfment function remains unknown. Here, we identified the C. elegans E3 ubiquitin ligase tripartite motif containing-21 (TRIM-21) as a component of the CED-1 pathway for apoptotic cell clearance. When the NPXY motif of CED-1 was bound to the adaptor protein CED-6 or the YXXL motif of CED-1 was phosphorylated by tyrosine kinase SRC-1 and subsequently bound to the adaptor protein NCK-1 containing the SH2 domain, TRIM-21 functioned in conjunction with UBC-21 to catalyze K48-linked poly-ubiquitination on CED-1, targeting it for proteasomal degradation. In the absence of TRIM-21, CED-1 accumulated post-translationally and drove cell corpse degradation defects, as evidenced by direct binding to VHA-10. These findings reveal a unique mechanism for the maintenance of appropriate levels of CED-1 to regulate apoptotic cell clearance.