Proteomic analysis of the secretome of Leishmania donovani.
Proteomic analysis of the secretome of Leishmania donovani.
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Leishmania Donovani分泌蛋白质组学分析。
DOI：
10.1186/gb-2008-9-2-r35
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发表时间：
2008
期刊：
影响因子：
12.3
通讯作者：
Reiner, Neil E.
中科院分区：
文献类型：
--
作者：
Silverman, J. Maxwell;Chan, Simon K.;Robinson, Dale P.;Dwyer, Dennis M.;Nandan, Devki;Foster, Leonard J.;Reiner, Neil E.
利什曼原虫条件培养基的分析导致151蛋白的鉴定显然分泌的寄生原虫杜氏利什曼原虫，并建议囊泡为基础的分泌系统。利什曼原虫和其他细胞内病原体已经进化出支持宿主靶细胞内的入侵和持久性的策略。在某些情况下，潜在的机制涉及毒力因子输出到宿主细胞胞质溶胶中。我们实验室以前的工作确定了一种这样的候选利什曼原虫效应子，即延伸因子-1 α，存在于感染性利什曼原虫的条件培养基中以及感染后的巨噬细胞胞质溶胶中。为了更广泛地研究潜在效应物的分泌，我们使用定量质谱法分析收集自杜氏利什曼原虫（内脏利什曼病的一种媒介）的静止期前鞭毛体培养物的条件培养基的蛋白质含量。对利什曼原虫条件培养基的分析鉴定出151个明显由利什曼原虫分泌的蛋白质。donovani。反映每种利什曼原虫蛋白质分泌的相对量的比率，与剩余的相关细胞相比，揭示了蛋白质分泌的层次结构，其中一些蛋白质的分泌程度高于其他蛋白质。与计算机方法定义蛋白质可能出口沿着经典的真核分泌途径的比较表明，很少有利什曼原虫蛋白质是针对出口使用一个经典的真核氨基末端分泌信号肽。出乎意料的是，在利什曼原虫条件培养基中检测到绝大多数已知的真核外泌体蛋白，表明基于囊泡的分泌系统。结果表明，L. Donovani是一种不均匀的过程，不太可能由经典的氨基末端分泌信号决定。作为替代，L. donovani似乎使用多种非经典分泌途径，包括释放外泌体样微泡。
Analysis of Leishmania-conditioned medium resulted in the identification of 151 proteins apparently secreted by the parasitic protozoan Leishmania donovani and suggested a vesicle-based secretion system. Leishmania and other intracellular pathogens have evolved strategies that support invasion and persistence within host target cells. In some cases the underlying mechanisms involve the export of virulence factors into the host cell cytosol. Previous work from our laboratory identified one such candidate leishmania effector, namely elongation factor-1α, to be present in conditioned medium of infectious leishmania as well as within macrophage cytosol after infection. To investigate secretion of potential effectors more broadly, we used quantitative mass spectrometry to analyze the protein content of conditioned medium collected from cultures of stationary-phase promastigotes of Leishmania donovani, an agent of visceral leishmaniasis. Analysis of leishmania conditioned medium resulted in the identification of 151 proteins apparently secreted by L. donovani. Ratios reflecting the relative amounts of each leishmania protein secreted, as compared to that remaining cell associated, revealed a hierarchy of protein secretion, with some proteins secreted to a greater extent than others. Comparison with an in silico approach defining proteins potentially exported along the classic eukaryotic secretion pathway suggested that few leishmania proteins are targeted for export using a classic eukaryotic amino-terminal secretion signal peptide. Unexpectedly, a large majority of known eukaryotic exosomal proteins was detected in leishmania conditioned medium, suggesting a vesicle-based secretion system. This analysis shows that protein secretion by L. donovani is a heterogeneous process that is unlikely to be determined by a classical amino-terminal secretion signal. As an alternative, L. donovani appears to use multiple nonclassical secretion pathways, including the release of exosome-like microvesicles.
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影响因子：
3.1
作者：
Chen, DQ;Kolli, BK;Chang, KP
通讯作者：
Chang, KP
影响因子：
3.4
作者：
Colasante, Claudia;Ellis, Margrit;Voncken, Frank
通讯作者：
Voncken, Frank
影响因子：
--
作者：
Costa, CHN;Werneck, GL;Lima, SS
通讯作者：
Lima, SS
影响因子：
2.1
作者：
BATES, PA;GOTTLIEB, M;DWYER, DM
通讯作者：
DWYER, DM
影响因子：
3.7
作者：
Carvalho, LP;Passos, S;de Jesus, AR
通讯作者：
de Jesus, AR