A novel alternate secretory pathway for the export of Plasmodium proteins into the host erythrocyte.
The malarial parasite dramatically alters its host cell by exporting and targeting proteins to specific locations within the erythrocyte. Little is known about the mechanisms by which the parasite is able to carry out this extraparasite transport. The fungal metabolite brefeldin A (BFA) has been used to study the secretory pathway in eukaryotes. BFA treatment of infected erythrocytes inhibits protein export and results in the accumulation of exported Plasmodium proteins into a compartment that is at the parasite periphery. Parasite proteins that are normally localized to the erythrocyte membrane, to nonmembrane bound inclusions in the erythrocyte cytoplasm, or to the parasitophorous vacuolar membrane accumulate in this BFA-induced compartment. A single BFA-induced compartment is detected per parasite and the various exported proteins colocalize to this compartment regardless of their final destinations. Parasite membrane proteins do not accumulate in this novel compartment, but accumulate in the endoplasmic reticulum (ER), suggesting that the parasite has two secretory pathways. This alternate secretory pathway is established immediately after merozoite invasion and at least some dense granule proteins also use the alternate pathway. The BFA-induced compartment exhibits properties that are similar to the ER, but it is clearly distinct from the ER. We propose to call this new organelle the secondary ER of apicomplexa. This ER-like organelle is an early, if not the first, step in the export of Plasmodium proteins into the host erythrocyte.
Wiser
M F
MF
Department of Tropical Medicine, Tulane University School of Public Health, New Orleans, LA 70112, USA. wiser@mailhost.tulane.edu
Lanners
H N
HN
Bafford
R A
RA
Favaloro
J M
JM
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D020126:Brefeldin A; D003517:Cyclopentanes / Q000494:pharmacology; D004912:Erythrocytes / Q000469:parasitology*; D006790:Host-Parasite Interactions; D007150:Immunohistochemistry; D051379:Mice; D010961:Plasmodium / Q000378:metabolism* / Q000469:parasitology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015800:Protozoan Proteins / Q000378:metabolism*; D015398:Signal Transduction
D003517:Cyclopentanes; D011500:Protein Synthesis Inhibitors; D015800:Protozoan Proteins; D020126:Brefeldin A