Phosphatidylinositol 4-phosphate and phosphatidylinositol 3-phosphate regulate phagolysosome biogenesis
Phosphatidylinositol 4-phosphate and phosphatidylinositol 3-phosphate regulate phagolysosome biogenesis
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DOI：
10.1073/pnas.1423456112
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发表时间：
2015-04-14
影响因子：
11.1
通讯作者：
Haas, Albert
中科院分区：
文献类型：
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作者：
Jeschke, Andreas;Zehethofer, Nicole;Haas, Albert
专业吞噬细胞通过吞噬侵入的微生物进入吞噬体，吞噬体随后成熟为杀微生物吞噬溶酶体。吞噬体的成熟需要吞噬体与早期内体、晚期内体和溶酶体的顺序融合。尽管在吞噬体上检测到多种磷酸肌苷（PIPs），但目前尚不清楚哪些PIPs实际上控制吞噬体的成熟。在这里，我们分析了PIPs参与吞噬体与各种内吞室的融合，并确定了磷脂酰肌醇4-磷酸[PI(4)P]，磷脂酰肌醇3-磷酸[PI(3)P]，以及产生这些PIPs的脂质激酶，作为吞噬体-溶酶体融合的介质。吞噬体-早期核内体融合需要PI(3)P，但不依赖于PI(4)P。因此，PI(3)P在早期和晚期调控吞噬体成熟，而PI(4)P在该途径的晚期是选择性需要的。
Professional phagocytic cells ingest microbial intruders by engulfing them into phagosomes, which subsequently mature into microbicidal phagolysosomes. Phagosome maturation requires sequential fusion of the phagosome with early endosomes, late endosomes, and lysosomes. Although various phosphoinositides (PIPs) have been detected on phagosomes, it remained unclear which PIPs actually govern phagosome maturation. Here, we analyzed the involvement of PIPs in fusion of phagosomes with various endocytic compartments and identified phosphatidylinositol 4-phosphate [PI(4)P], phosphatidylinositol 3-phosphate [PI(3)P], and the lipid kinases that generate these PIPs, as mediators of phagosome-lysosome fusion. Phagosome-early endosome fusion required PI(3)P, yet did not depend on PI(4)P. Thus, PI(3)P regulates phagosome maturation at early and late stages, whereas PI(4)P is selectively required late in the pathway.