Endoplasmic Reticulum PI(3)P Lipid Binding Targets Malaria Proteins to the Host Cell

被引:98
作者
Bhattacharjee, Souvik [1 ,2 ]
Stahelin, Robert V. [3 ,4 ]
Speicher, Kaye D. [5 ,6 ]
Speicher, David W. [5 ,6 ]
Haldar, Kasturi [1 ,2 ]
机构
[1] Univ Notre Dame, Ctr Rare & Neglected Dis, Notre Dame, IN 46556 USA
[2] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA
[3] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA
[4] Indiana Univ Sch Med, Dept Biochem & Mol Biol, South Bend, IN 46617 USA
[5] Wistar Inst Anat & Biol, Ctr Syst & Computat Biol, Philadelphia, PA 19104 USA
[6] Wistar Inst Anat & Biol, Mol & Cellular Oncogenesis Program, Philadelphia, PA 19104 USA
关键词
RED-BLOOD-CELLS; PLASMODIUM-FALCIPARUM; EFFECTOR PROTEINS; ERYTHROCYTE; PARASITES; VIRULENCE; SIGNAL; EXPORT; ORGANIZATION; MEMBRANE;
D O I
10.1016/j.cell.2011.10.051
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hundreds of effector proteins of the human malaria parasite Plasmodium falciparum constitute a "secretome" carrying a host-targeting (HT) signal, which predicts their export from the intracellular pathogen into the surrounding erythrocyte. Cleavage of the HT signal by a parasite endoplasmic reticulum (ER) protease, plasmepsin V, is the proposed export mechanism. Here, we show that the HT signal facilitates export by recognition of the lipid phosphatidylinositol-3-phosphate (PI(3)P) in the ER, prior to and independent of protease action. Secretome HT signals, including those of major virulence determinants, bind PI(3)P with nanomolar affinity and amino acid specificities displayed by HT-mediated export. PI(3)P-enriched regions are detected within the parasite's ER and colocalize with endogenous HT signal on ER precursors, which also display high-affinity binding to PI(3)P. A related pathogenic oomycete's HT signal export is dependent on PI(3)P binding, without cleavage by plasmepsin V. Thus, PI(3)P in the ER functions in mechanisms of secretion and pathogenesis.
引用
收藏
页码:201 / 212
页数:12
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