Host targeting of virulence determinants and phosphoinositides in blood stage malaria parasites.
Blood stage malaria parasites target a 'secretome' of hundreds of proteins including virulence determinants containing a host (cell) targeting (HT) signal, to human erythrocytes. Recent studies reveal that the export mechanism is due to the HT signal binding to the lipid phosphatidylinositol-3-phosphate [PI(3)P] in the parasite endoplasmic reticulum (ER). An aspartic protease plasmepsin V which cleaves a specialized form of the HT signal was previously thought to be the export mechanism, but is now recognized as a dedicated peptidase that cleaves the signal anchor subsequent to PI(3)P binding. We discuss a model of PI(3)P-dependent targeting and PI(3)P biology of a major human pathogen.
Center for Rare and Neglected Diseases, University of Notre Dame, 103 Galvin Life Sciences, Notre Dame, IN 46556, USA.
Souvik
S
Bhattacharjee
Robert V
RV
Stahelin
Kasturi
K
Haldar
D004721:Endoplasmic Reticulum / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology; D054884:Host-Pathogen Interactions; D006801:Humans; D016778:Malaria, Falciparum / Q000378:metabolism / Q000469:parasitology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000201:enzymology / Q000378:metabolism* / Q000472:pathogenicity*; D015800:Protozoan Proteins / Q000378:metabolism; D037521:Virulence Factors / Q000378:metabolism*
D010716:Phosphatidylinositols; D015800:Protozoan Proteins; D037521:Virulence Factors; D019869:Phosphatidylinositol 3-Kinases