Syk facilitates phagosome-lysosome fusion by regulating actin-remodeling in complement-mediated phagocytosis.
Syk facilitates phagosome-lysosome fusion by regulating actin-remodeling in complement-mediated phagocytosis.
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SYK通过调节肌动蛋白在补体介导的吞噬作用中调节肌动蛋白转换来促进吞噬体溶酶体融合。
DOI：
10.1038/s41598-020-79156-7
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发表时间：
2020-12-16
影响因子：
4.6
通讯作者：
Tohyama Y
中科院分区：
文献类型：
--
作者：
Tabata H;Morita H;Kaji H;Tohyama K;Tohyama Y
有效的吞噬作用对于宿主防御病原体至关重要。巨噬细胞将病原体捕获到吞噬体中，随后酸性溶酶体与吞噬体融合。以往的研究表明，磷酸肌醇相关信号介导的肌动蛋白重构在吞噬体形成中起着关键作用，但吞噬体-溶酶体融合的机制尚不清楚。在这里，我们表明，在补体介导的吞噬作用，吞噬体-溶酶体融合需要周围的吞噬体和酪氨酸激酶Syk的F-肌动蛋白结构的消失在这个过程中起着关键作用。使用巨噬细胞样分化的HL 60和Syk敲除（Syk-KO）HL 60细胞，我们发现Syk-KO细胞表现出与溶酶体融合受损引起的吞噬体酸化不足，并允许白色念珠菌在补体介导的吞噬作用中存活。吞噬体追踪分析表明，在吞噬体内化过程中，亲本细胞和Syk-KO细胞中吞噬体周围的F-肌动蛋白均消失，但仅Syk-KO细胞中这种结构立即重建。此外，F-肌动蛋白稳定剂诱导吞噬体-溶酶体融合的类似损害。总的来说，Syk衍生的信号通过调节肌动蛋白重塑促进吞噬体-溶酶体融合。
Effective phagocytosis is crucial for host defense against pathogens. Macrophages entrap pathogens into a phagosome and subsequently acidic lysosomes fuse to the phagosome. Previous studies showed the pivotal role of actin-remodeling mediated by phosphoinositide-related signaling in phagosome formation, but the mechanisms of phagosome-lysosome fusion remain unexplored. Here we show that in complement-mediated phagocytosis, phagosome-lysosome fusion requires the disappearance of F-actin structure surrounding the phagosome and a tyrosine kinase Syk plays a key role in this process. Using macrophage-like differentiated HL60 and Syk-knockout (Syk-KO) HL60 cells, we found that Syk-KO cells showed insufficient phagosome acidification caused by impaired fusion with lysosomes and permitted the survival of Candida albicans in complement-mediated phagocytosis. Phagosome tracking analysis showed that during phagosome internalization process, F-actin surrounding phagosomes disappeared in both parental and Syk-KO cells but this structure was reconstructed immediately only in Syk-KO cells. In addition, F-actin-stabilizing agent induced a similar impairment of phagosome-lysosome fusion. Collectively, Syk-derived signaling facilitates phagosome-lysosome fusion by regulating actin-remodeling.
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影响因子：
11.8
作者：
Jaumouille, Valentin;Farkash, Yoav;Jaqaman, Khuloud;Das, Raibatak;Lowell, Clifford A.;Grinstein, Sergio
通讯作者：
Grinstein, Sergio
基于磷脂酰肌醇 4,5-二磷酸重新分布的传感机制启动吞噬程序
影响因子：
16.6
作者：
Mu L;Tu Z;Miao L;Ruan H;Kang N;Hei Y;Chen J;Wei W;Gong F;Wang B;Du Y;Ma G;Amerein MW;Xia T;Shi Y
通讯作者：
Shi Y
影响因子：
2.1
作者：
Hazama, Ryoichi;Qu, Xiujuan;Tohyama, Yumi
通讯作者：
Tohyama, Yumi
影响因子：
2.1
作者：
He, J;Tohyama, Y;Yamamura, H
通讯作者：
Yamamura, H
影响因子：
20.3
作者：
Shi, Yuhong;Tohyama, Yumi;Yamamura, Hirohei
通讯作者：
Yamamura, Hirohei