The phagosome proteome: insight into phagosome functions.
The phagosome proteome: insight into phagosome functions.
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吞噬体蛋白质组：洞察吞噬体功能。
DOI：
10.1083/jcb.152.1.165
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发表时间：
2001-01-08
影响因子：
7.8
通讯作者：
Desjardins, M
中科院分区：
文献类型：
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作者：
Garin, J;Diez, R;Kieffer, S;Dermine, J F;Duclos, S;Gagnon, E;Sadoul, R;Rondeau, C;Desjardins, M
吞噬体是巨噬细胞参与组织重塑、清除凋亡细胞和限制细胞内病原体扩散的先天能力的关键细胞器。为了了解吞噬体的功能，我们开始了对其蛋白质的系统鉴定。使用蛋白质组学方法，我们鉴定了>140种与含乳胶珠的吞噬体相关的蛋白质。其中包括水解酶、质子泵ATP酶亚基和融合机制的蛋白质，验证了我们的方法。还鉴定了一系列先前未描述的沿着内吞/吞噬途径的意想不到的蛋白质，包括凋亡蛋白半乳糖凝集素3、阿利克斯和TRAIL、抗凋亡蛋白14-3-3、脂质筏富集的flotillin-1、抗微生物分子lactadherin和小GTcirab 14。此外，24个点的肽质量不能匹配任何数据库中的条目可能代表新的吞噬体蛋白。一个二维凝胶数据库的详细说明>160个识别的斑点，使我们能够分析吞噬体组成是如何调节在吞噬溶酶体生物发生。值得注意的是，在这个过程中，水解酶不是批量递送到吞噬体，而是顺序获得。吞噬体蛋白质的系统表征为吞噬体功能以及参与和调节这些功能的蛋白质或蛋白质组提供了新的见解。
Phagosomes are key organelles for the innate ability of macrophages to participate in tissue remodeling, clear apoptotic cells, and restrict the spread of intracellular pathogens. To understand the functions of phagosomes, we initiated the systematic identification of their proteins. Using a proteomic approach, we identified >140 proteins associated with latex bead–containing phagosomes. Among these were hydrolases, proton pump ATPase subunits, and proteins of the fusion machinery, validating our approach. A series of unexpected proteins not previously described along the endocytic/phagocytic pathways were also identified, including the apoptotic proteins galectin3, Alix, and TRAIL, the anti-apoptotic protein 14-3-3, the lipid raft-enriched flotillin-1, the anti-microbial molecule lactadherin, and the small GTPase rab14. In addition, 24 spots from which the peptide masses could not be matched to entries in any database potentially represent new phagosomal proteins. The elaboration of a two-dimensional gel database of >160 identified spots allowed us to analyze how phagosome composition is modulated during phagolysosome biogenesis. Remarkably, during this process, hydrolases are not delivered in bulk to phagosomes, but are instead acquired sequentially. The systematic characterization of phagosome proteins provided new insights into phagosome functions and the protein or groups of proteins involved in and regulating these functions.