Autophagy proteins are not universally required for phagosome maturation
Autophagy proteins are not universally required for phagosome maturation
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DOI：
10.1080/15548627.2016.1191724
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发表时间：
2016-01-01
期刊：
影响因子：
13.3
通讯作者：
Brumell, John H.
中科院分区：
文献类型：
--
作者：
Cemma, Marija;Grinstein, Sergio;Brumell, John H.
吞噬作用在免疫和组织稳态中起核心作用。在货物内化到单膜吞噬体中后，这些隔室经历成熟序列，其终止于溶酶体融合和货物降解。自噬途径的成分最近被链接到吞噬体成熟的过程中称为LC 3相关的吞噬作用（ESTA）。在这个过程中，自噬机制被认为将LC 3直接缀合到吞噬体膜上以促进溶酶体融合。然而，最近的一项研究表明，ATG蛋白实际上可能会损害吞噬体的成熟，以促进抗原呈递。在这里，我们使用FCGR 2A/FcR依赖性吞噬作用作为模型，研究了ATG蛋白对小鼠细胞中吞噬体成熟的影响。我们发现，吞噬体成熟不受影响，在Atg 5缺陷的小鼠胚胎成纤维细胞，或在Atg 5或Atg 7缺陷的骨髓来源的巨噬细胞使用标准的吞噬体成熟测定。我们建议，ATG蛋白可能需要吞噬体成熟在某些条件下，但并不普遍需要这个过程。
Phagocytosis plays a central role in immunity and tissue homeostasis. After internalization of cargo into single-membrane phagosomes, these compartments undergo a maturation sequences that terminates in lysosome fusion and cargo degradation. Components of the autophagy pathway have recently been linked to phagosome maturation in a process called LC3-associated phagocytosis (LAP). In this process, autophagy machinery is thought to conjugate LC3 directly onto the phagosomal membrane to promote lysosome fusion. However, a recent study has suggested that ATG proteins may in fact impair phagosome maturation to promote antigen presentation. Here, we examined the impact of ATG proteins on phagosome maturation in murine cells using FCGR2A/FcR-dependent phagocytosis as a model. We show that phagosome maturation is not affected in Atg5-deficient mouse embryonic fibroblasts, or in Atg5- or Atg7-deficient bone marrow-derived macrophages using standard assays of phagosome maturation. We propose that ATG proteins may be required for phagosome maturation under some conditions, but are not universally required for this process.