The transport of the histidine-rich protein I from Plasmodium falciparum is insensitive to brefeldin A.
During its intraerythrocytic development, Plasmodium falciparum synthesizes several proteins that are exported beyond its membrane. Some of these secreted antigens are involved in the formation of protuberances or knobs, a major virulence factor, at the erythrocyte membrane. Various secreted malarial polypeptides, the transport of which is sensitive to brefeldin A, are translocated in vitro into dog pancreatic microsomes. We present evidence that the histidine-rich protein I (PfHRPI) is secreted by the parasite via a novel pathway, independent of the ER/Golgi apparatus. The secretion of PfHRPI was not blocked by incubation of parasite cultures at 15 degrees C and 20 degrees C or 37 degrees C in the presence of brefeldin A. PfHRPI was not translocated into microsomes in an in vitro translation-translocation cell-free system. Unlike other polypeptides from eukaryotic cells that bypass the ER/Golgi pathway and do not have a signal peptide, PfHRPI has an atypical signal sequence consisting of 21 amino acids, including eight positively charged residues followed by 11 hydrophobic residues. We also found that the unusually charged PfHRPI signal sequence diverts Exp-1, which is usually exported, away from the translocation machinery of microsomal membranes.
Mattei
D
D
Unit of Biology of Host-Parasite Interactions, CNRS URA 1960, Institute Pasteur, Paris, France.
Berry
L
L
Couffin
S
S
Richard
O
O
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D020126:Brefeldin A / Q000494:pharmacology*; D004285:Dogs; D006639:Histidine; D008861:Microsomes / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D000099053:Histidine-Rich Glycoprotein
D011500:Protein Synthesis Inhibitors; D011506:Proteins; D015800:Protozoan Proteins; D000099053:Histidine-Rich Glycoprotein; D020126:Brefeldin A; D006639:Histidine