CED-10-WASP-Arp2/3 signaling axis regulates apoptotic cell corpse engulfment in C. elegans
CED-10-WASP-Arp2/3 signaling axis regulates apoptotic cell corpse engulfment in C. elegans
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CED-10-WASP-Arp2/3信号轴调节线虫凋亡细胞尸体吞噬
DOI：
10.1016/j.ydbio.2017.06.005
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发表时间：
2017
影响因子：
2.7
通讯作者：
Li Wei
中科院分区：
文献类型：
--
作者：
Wu Dou;Chai Yongping;Zhu Zhiwen;Li Wenjing;Ou Guangshuo;Li Wei
凋亡细胞的有效清除对于后生动物的组织稳态是必不可少的。对秀丽隐杆线虫的遗传学研究已经确定了在凋亡细胞吞噬过程中激活CED-10/Rac 1 GT3并促进肌动蛋白细胞骨架重排的信号级联。然而，CED-10激活和肌动蛋白重组之间的分子联系仍然难以捉摸。在这里，我们提供的证据表明，CED-10结合Arp 2/3成核促进因子WASP; CED-10招募WASP和Arp 2/3吞噬细胞中的凋亡细胞尸体。WASP和Arp 2/3的缺失损害了细胞尸体吞噬。此外，我们发现，WASP激活因子SEM-5/GRB 2的功能，在吞噬细胞，以促进细胞尸体清除。总之，我们的研究结果表明，CED-10重组肌动蛋白细胞骨架的招募WASP-Arp 2/3肌动蛋白成核因子在凋亡细胞吞噬。
Efficient clearance of apoptotic cells is essential for tissue homeostasis in metazoans. Genetic studies inCaenorhabditis eleganshave identified signaling cascades that activate CED-10/Rac1 GTPase and promote actin cytoskeletal rearrangement during apoptotic cell engulfment. However, the molecular connection between CED-10 activation and actin reorganization remains elusive. Here, we provide evidence that CED-10 binds to the Arp2/3 nucleation promoting factor WASP; CED-10 recruits WASP and Arp2/3 to apoptotic cell corpses in the phagocytes. The loss of WASP and Arp2/3 impaired cell corpse engulfment. Furthermore, we uncover that a WASP-activating factor SEM-5/GRB2 functions in the phagocytes to promote cell corpse clearance. Together, our results suggest CED-10 reorganizes the actin cytoskeleton by recruiting the WASP-Arp2/3 actin nucleation factors during apoptotic cell engulfment.