Rho-kinase and myosin-II control phagocytic cup formation during CR, but not FcγR, phagocytosis
Rho-kinase and myosin-II control phagocytic cup formation during CR, but not FcγR, phagocytosis
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DOI：
10.1016/s0960-9822(02)01069-2
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发表时间：
2002-08-20
期刊：
影响因子：
9.2
通讯作者：
Machesky, LM
中科院分区：
文献类型：
--
作者：
Olazabal, IM;Caron, E;Machesky, LM
通过FcGamma受体(FcGammaR)或补体受体3(CR)吞噬细胞需要Arp2/3复合体介导的肌动蛋白聚合，尽管每个受体使用不同的信号通路[1]。在FcGammaR吞噬过程中，肌动蛋白和Arp2/3复合体的募集需要Rac和CDC42，而Rho控制着肌动蛋白在CR吞噬小体的组装[2，3]。为了更好地了解Rho在CR吞噬作用中的作用，我们测试了Rho的已知靶点Rho-Kinase(ROK)可能控制吞噬杯形成和/或颗粒吞噬的想法。韩国(显性阴性的韩国和Y-27632)和韩国下游靶标肌球蛋白-II(ML7、BDM和显性阴性的肌球蛋白-II)的抑制剂被用来检验这一观点。我们发现，抑制Rho-->；ROK-->；myosin-II途径导致Arp2/3复合体和F-肌动蛋白在结合颗粒周围聚集减少，从而导致CR介导的吞噬减少。相反，FcGammaR介导的吞噬作用不依赖于Rho或韩国的活性，只依赖于肌球蛋白II的颗粒内化，而不是肌动蛋白杯的形成。虽然肌球蛋白以前被认为与FcGammaR吞噬作用有关[4-6]，但据我们所知，这是肌球蛋白-II在CR吞噬作用中作用的第一次证明。
Phagocytosis through Fcgamma receptor (FcgammaR) or complement receptor 3 (CR) requires Arp2/3 complex-mediated actin polymerization, although each receptor uses a distinct signaling pathway [1]. Rac and Cdc42 are required for actin and Arp2/3 complex recruitment during FcgammaR phagocytosis, while Rho controls actin assembly at CR phagosomes [2, 3]. To better understand the role of Rho in CR phagocytosis, we tested the idea that a known target of Rho, Rho-kinase (ROK), might control phagocytic cup formation and/or engulfment of particles. Inhibitors of ROK (dominant-negative ROK and Y-27632) and of the downstream target of ROK, myosin-II (ML7, BDM, and dominant-negative myosin-II), were used to test this idea. We found that inhibition of the Rho --> ROK --> myosin-II pathway caused a decreased accumulation of Arp2/3 complex and F-actin around bound particles, which led to a reduction in CR-mediated phagocytic engulfment. FcgammaR-mediated phagocytosis, in contrast, was independent of Rho or ROK activity and was only dependent: on myosin-II for particle internalization, not for actin cup formation. While myosins have been previously implicated in FcgammaR phagocytosis [4-6]; to our knowledge; this is the first demonstration of a role for myosin-II in CR phagocytosis.