A novel alternate secretory pathway for the export of Plasmodium proteins into the host erythrocyte

A novel alternate secretory pathway for the export of Plasmodium proteins into the host erythrocyte

^*Department of Tropical Medicine, Tulane University School of Public Health, New Orleans, LA 70112; ^‡Tulane Regional Primate Research Center, Covington, LA 70433; and ^§Department of Medicine, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia

Communicated by William Trager, Rockefeller University, New York, NY (received for review March 28, 1997)

Abstract

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.

Footnotes

↵ † To whom reprint requests should be addressed at: Department of Tropical Medicine, Tulane University Medical Center, 1501 Canal Street, New Orleans, LA 70112. e-mail: wiser{at}mailhost.tcs.tulane.edu.
↵ ¶ The GenBank accession numbers for the five sequences are U80896, M34947, M25248, L19784, and M95789.
ABBREVIATIONS:

BFA,

brefeldin A;

ER,

endoplasmic reticulum;

MSP-1,

merozoite surface protein-1;

PVM,

parasitophorous vacuolar membrane;

sERA,

secondary ER of the apicomplexa;

TVM,

tubovesicular membrane