An alternate secretory pathway in Plasmodium: more questions than answers

Mark F. Wiser

The malaria parasite extensively modifies the host erythrocyte. Many of these modifications are mediated by proteins that are exported from the parasite and targeted to specific locations within the infected erythrocyte. However, little is known about how the parasite targets proteins to specific locations beyond its own plasma membrane. Treatment of infected erythrocytes with brefeldin-A results in the accumulation of many exported Plasmodium proteins into a compartment that is distinct from the endoplasmic reticulum. Proteins destined for the host erythrocyte membrane, the parasitophorous vacuole, or inclusions within the erythrocyte cytoplasm accumulate in this novel compartment and co-localization studies indicate that there is a single compartment per parasite. Exported proteins only accumulate in this novel compartment if brefeldin-A treatment is concurrent with their synthesis. This novel compartment is probably a membrane-bound organelle located at the parasite periphery and may be the first step in an alternate secretory pathway which specializes in the export of proteins into the host cell. Such an alternate secretory pathway raises questions about how exported proteins are differentially targeted to this novel organelle versus the endoplasmic reticulum, the fate of exported proteins after this novel organelle, and the origins of this novel organelle.

Department of Tropical Medicine, Tulane University School of Public Health and Tropical Medicine, 1501 Canal Street, New Orleans, LA 70112 U.S.A.