Erythrocyte detergent-resistant membrane proteins: their characterization and selective uptake during malarial infection
Erythrocyte detergent-resistant membrane proteins: their characterization and selective uptake during malarial infection
复制标题
DOI：
10.1182/blood-2003-09-3165
复制
发表时间：
2004-03-01
期刊：
影响因子：
20.3
通讯作者：
Haldar, K
中科院分区：
文献类型：
--
作者：
Murphy, SC;Samuel, BU;Haldar, K
人类红细胞被顶复门疟疾寄生虫恶性疟原虫感染，导致包膜吸收驻留在红细胞去污剂抗性膜 (DRM) 中的 4 种宿主蛋白。这种液泡运输是否反映了宿主 DRM 蛋白的选择性摄取仍不清楚。更复杂的是，从红细胞中分离出的 DRM 的蛋白质和胆固醇含量差异很大。在这里，我们表明，含有最高胆固醇与蛋白质比率的分离 DRM 具有较低的蛋白质质量。液相色谱、质谱和基于抗体的研究表明，主要的 DRM 蛋白是带 3、flotillin-1 和 -2、peroxiredoxin-2 和 sotomatin。带 3 和气孔蛋白反映了红细胞 DRM 蛋白的大量质量，所有测试的非 DRM 蛋白均被排除在液泡寄生虫之外。相反，flotillin-1 和-2 以及 8 个次要 DRM 蛋白被募集到液泡中。这些数据表明，DRM 关联对于液泡募集是必要的，但还不够，并且宿主 DRM 蛋白的子集存在活跃的液泡摄取。最后，10种内化的DRM蛋白显示出不同的脂质和肽锚，这表明与顶复体液泡形成的流行模型相反，DRM关联而不是脂质锚提供了蛋白质招募到疟疾液泡的首选标准。 (C) 2004 年，美国血液学会。
Infection of human erythrocytes by the apicomplexan malaria parasite Plasmodium falciparum results in enclovacuolar uptake of 4 host proteins that reside in erythrocyte detergent-resistant membranes (DRMs). Whether this vacuolar transport reflects selective uptake of host DRM proteins remains unknown. A further complication is that DRMs of vastly different protein and cholesterol contents have been isolated from erythrocytes. Here we show that isolated DRMs containing the highest cholesterol-to-protein ratio have low protein mass. Liquid chromatography, mass spectrometry, and antibody-based studies reveal that the major DRM proteins are band 3, flotillin-1 and -2, peroxiredoxin-2, and stomatin. Band 3 and stomatin, which reflect the bulk mass of erythrocyte DRM proteins, and all tested non-DRM proteins are excluded from the vacuolar parasite. In contrast, flotillin-1 and -2 and 8 minor DRM proteins are recruited to the vacuole. These data suggest that DRM association is necessary but not sufficient for vacuolar recruitment and there is active, vacuolar uptake of a subset of host DRM proteins. Finally, the 10 internalized DRM proteins show varied lipid and peptidic anchors indicating that, contrary to the prevailing model of apicomplexan vacuole formation, DRM association, rather than lipid anchors, provides the preferred criteria for protein recruitment to the malarial vacuole. (C) 2004 by The American Society of Hematology.