SNX3 recruits to phagosomes and negatively regulates phagocytosis in dendritic cells
SNX3 recruits to phagosomes and negatively regulates phagocytosis in dendritic cells
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DOI：
10.1111/imm.12051
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发表时间：
2013-05-01
期刊：
影响因子：
6.4
通讯作者：
Wong, Siew Heng
中科院分区：
文献类型：
--
作者：
Chua, Rong Yuan Ray;Wong, Siew Heng
巨噬细胞如树突状细胞（DC）和巨噬细胞利用吞噬作用将病原性细菌摄取到吞噬体中，消化细菌并将细菌衍生的肽抗原呈递给适应性免疫。因此，有效的抗原呈递在很大程度上取决于良好调节的吞噬过程。脂质，特别是磷酸肌醇，是吞噬体的关键组分。磷脂酰肌醇-3，4，5-三磷酸[PI（3，4，5）P3]在吞噬杯处形成，并且随着吞噬体从质膜封闭，PI（3，4，5）P3的快速消失伴随着高水平的磷脂酰肌醇-3-磷酸（PI 3 P）形成。分选连接蛋白（SNX）家族由一组不同的含有Phox同源（PX）结构域的细胞质和膜相关蛋白组成，这些蛋白是磷酸肌醇的潜在效应物。我们假设SNX 3是一种小的分选连接蛋白，包含一个单一的PI 3 P脂质结合PX结构域作为其唯一的蛋白结构域，定位于吞噬体并调节DC的吞噬作用。我们的研究结果表明，SNX 3招募新生的吞噬体和沉默SNX 3增强了DC的细菌吞噬摄取。此外，SNX 3与PI 3 P脂质结合蛋白竞争，早期内体抗原-1（EEA 1）募集到膜上。我们的研究结果表明，SNX 3负调节DC中的吞噬作用可能通过调节吞噬途径的必需PI 3 P脂质结合蛋白（如EEA 1）向吞噬体膜的募集。
Phagocytes such as dendritic cells (DC) and macrophages employ phagocytosis to take up pathogenic bacteria into phagosomes, digest the bacteria and present the bacteria-derived peptide antigens to the adaptive immunity. Hence, efficient antigen presentation depends greatly on a well-regulated phagocytosis process. Lipids, particularly phosphoinositides, are critical components of the phagosomes. Phosphatidylinositol-3,4,5-triphosphate [PI(3,4,5)P3] is formed at the phagocytic cup, and as the phagosome seals off from the plasma membrane, rapid disappearance of PI(3,4,5)P3 is accompanied by high levels of phosphatidylinositol-3-phosphate (PI3P) formation. The sorting nexin (SNX) family consists of a diverse group of Phox-homology (PX) domain-containing cytoplasmic and membrane-associated proteins that are potential effectors of phosphoinositides. We hypothesized that SNX3, a small sorting nexin that contains a single PI3P lipid-binding PX domain as its only protein domain, localizes to phagosomes and regulates phagocytosis in DC. Our results show that SNX3 recruits to nascent phagosomes and silencing of SNX3 enhances phagocytic uptake of bacteria by DC. Furthermore, SNX3 competes with PI3P lipid-binding protein, early endosome antigen-1 (EEA1) recruiting to membranes. Our results indicate that SNX3 negatively regulates phagocytosis in DC possibly by modulating recruitment of essential PI3P lipid-binding proteins of the phagocytic pathways, such as EEA1, to phagosomal membranes.