CED-2/Crkll and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans
CED-2/Crkll and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans
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DOI：
10.1038/35004000
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发表时间：
2000-03-01
影响因子：
21.3
通讯作者：
Horvitz, HR
中科院分区：
文献类型：
--
作者：
Reddien, PW;Horvitz, HR
秀丽隐杆线虫中凋亡细胞的吞噬是由两条部分冗余的途径控制的。这些途径之一（由基因 ced-2、ced-5 和 ced-10 定义）中的基因突变会导致死亡细胞的吞噬和发育中性腺的两个远端细胞的迁移缺陷。在这里，我们发现 ced-2 和 ced-10 编码的蛋白质分别与人类衔接蛋白 Crkll 和人类 GTPase Rac 相似。结合之前对 ced-5 编码与人类 DOCK180 相似的蛋白质的观察，我们的发现定义了控制吞噬作用和细胞迁移的信号通路。我们提供的证据表明，CED-2 和 CED-10 的功能是吞噬而不是死亡细胞，以控制细胞尸体的吞噬作用，CED-2 和 CED-5 发生物理相互作用，并且 ced-10 可能在 ced-2 和 ced-5 的下游发挥作用。我们提出 CED-2/Crkll 和 CED-5/DOCK180 的功能是激活控制细胞表面极化延伸的 GTPase 信号通路中的 CED-10/Rac。
Engulfment of apoptotic cells in Caenorhabditis elegans is controlled by two partially redundant pathways. Mutations in genes in one of these pathways, defined by the genes ced-2, ced-5 and ced-10, result in defects both in the engulfment of dying cells and in the migrations of the two distal tip cells of the developing gonad. Here we find that ced-2 and ced-10 encode proteins similar to the human adaptor protein Crkll and the human GTPase Rac, respectively. Together with the previous observation that ced-5 encodes a protein similar to human DOCK180, our findings define a signalling pathway that controls phagocytosis and cell migration. We provide evidence that CED-2 and CED-10 function in engulfing rather than dying cells to control the phagocytosis of cell corpses, that CED-2 and CED-5 physically interact, and that ced-10 probably functions downstream of ced-2 and ced-5. We propose that CED-2/Crkll and CED-5/DOCK180 function to activate CED-10/Rac in a GTPase signalling pathway that controls the polarized extension of cell surfaces.