Identification of a stomatin orthologue in vacuoles induced in human erythrocytes by malaria parasites - A role for microbial raft proteins in apicomplexan vacuole biogenesis
Identification of a stomatin orthologue in vacuoles induced in human erythrocytes by malaria parasites - A role for microbial raft proteins in apicomplexan vacuole biogenesis
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DOI：
10.1074/jbc.m307266200
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发表时间：
2003-11-28
影响因子：
4.8
通讯作者：
Haldar, K
中科院分区：
文献类型：
--
作者：
Hiller, NL;Akompong, T;Haldar, K
当人类疟疾寄生虫恶性疟原虫感染红细胞时，与宿主衍生的抗去污剂膜（DRM）筏相关的蛋白质被选择性地招募到新形成的液泡中，但有助于基于筏的液泡发育的寄生虫蛋白尚不清楚。在哺乳动物细胞中，形成寡聚体的 DRM 相关整合膜蛋白（例如 Caveolin-1 和 flotillin-1）与基于 DRM 的内陷（称为小窝）的形成有关。在这里，我们表明，恶性疟原虫基因组不编码caveolins或flotillins，但确实含有人类带7 sotomatin的直系同源物，这是一种已知寡聚化的蛋白质，与非caveolar DRM相关，并且与flotillins有远亲关系。造口蛋白是进化中保守的一个大蛋白质家族的成员，恶性疟原虫（Pf）造口蛋白似乎是一种原核样分子。有证据表明它与 DRM 相关并且可能寡聚化，表明这些特征在造口蛋白家族中是保守的。此外，Pfstomatin 是一种整合膜蛋白，集中在细胞外寄生虫的顶端，与入侵相关的菱形细胞器共定位。 RhopH2 是一种常驻棒状体蛋白，也存在于 DRM 中。这提供了第一个证据表明顶端复门寄生虫的棒状体含有 DRM 筏。此外，当寄生虫侵入红细胞时，棒状体 Pfstomatin 和 RhopH2 会插入新形成的液泡中。因此，像 Caveolin-1 和 flotillin-1 一样，stomatin 也可能与非网格蛋白包被的、富含 DRM 的液泡相关联。我们提出了一种新的入侵和液泡形成模型，涉及宿主和寄生虫分子基于 DRM 的相互作用。
When the human malaria parasite Plasmodium falciparum infects erythrocytes, proteins associated with host-derived detergent-resistant membrane (DRM) rafts are selectively recruited into the newly formed vacuole, but parasite proteins that contribute to raft-based vacuole development are unknown. In mammalian cells, DRM-associated integral membrane proteins such as caveolin-1 and flotillin-1 that form oligomers have been linked to the formation of DRM-based invaginations called caveolae. Here we show that the P. falciparum genome does not encode caveolins or flotillins but does contain an orthologue of human band 7 stomatin, a protein known to oligomerize, associate with non-caveolar DRMs and is distantly related to flotillins. Stomatins are members of a large protein family conserved in evolution and P. falciparum (Pf) stomatin appears to be a prokaryotic-like molecule. Evidence is presented that it associates with DRMs and may oligomerize, suggesting that these features are conserved in the stomatin family. Further, Pfstomatin is an integral membrane protein concentrated at the apical end of extracellular parasites, where it co-localizes with invasion-associated rhoptry organelles. A resident rhoptry protein, RhopH2 also resides in DRMs. This provides the first evidence that rhoptries of an apicomplexan parasite contain DRM rafts. Further, when the parasite invades erythrocytes, rhoptry Pfstomatin and RhopH2 are inserted into the newly formed vacuole. Thus, like caveolin-1 and flotillin-1, a stomatin may also associate with non-clathrin coated, DRM-enriched vacuoles. We propose a new model of invasion and vacuole formation involving DRM-based interactions of both host and parasite molecules.