Abstract
The early transcribed membrane proteins ETRAMPs belong to a family of small, transmembrane molecules unique to Plasmodium parasite, which share a signal peptide followed by a short lysine-rich stretch, a transmembrane domain and a variable, highly charged C-terminal region. ETRAMPs are usually expressed in a stage-specific manner. In the blood stages they localize to the parasitophorous vacuole membrane and, in described cases, to vesicle-like structures exported to the host erythrocyte cytosol. Two family members of the rodent parasite Plasmodium berghei, uis3 and uis4, localize to secretory organelles of sporozoites and to the parasitophorous membrane vacuole of the liver stages. By the use of specific antibodies and the generation of transgenic lines, we showed that the P. berghei ETRAMP family member SEP2 is abundantly expressed in gametocytes as well as in mosquito and liver stages. In intracellular parasite stages, SEP2 is routed to the parasitophorous vacuole membrane while, in invasive ookinete and sporozoite stages, it localizes to the parasite surface. To date SEP2 is the only ETRAMP protein detected throughout the parasite life cycle. Furthermore, SEP2 is also released during gliding motility of salivary gland sporozoites. A limited number of proteins are known to be involved in this key function and the best characterized, the CSP and TRAP, are both promising transmission-blocking candidates. Our results suggest that ETRAMP members may be viewed as new potential candidates for malaria control.
Highlights
Malaria is one of the oldest and most frequently occurring infectious diseases in humans
SEP2 and SEP3 are Expressed in Blood Stages and Ookinetes
We analyzed the expression of sep2 and sep3 at different time points of a synchronous P. berghei infection, using specific mouse immune sera [21] raised against the variable C-terminal portions (Fig. 1A)
Summary
Malaria is one of the oldest and most frequently occurring infectious diseases in humans It is caused by Plasmodium parasite, an obligate intracellular protozoa transmitted through the bite of an infected female mosquito. In the vertebrate host the parasite either multiplies asexually or differentiates to sexual stages, the male and female gametocytes. These gamete precursors develop in the blood, but gametogenesis and gamete fertilization only takes place after the uptake of a blood meal by the mosquito. Sporozoites are injected into a mammalian host during a mosquito blood meal and are rapidly transported to the liver, where they invade the hepatocytes They multiply inside a parasitophorous vacuole (PV), resulting in the release of thousands of merozoites. These invade erythrocytes and the asexual multiplication in the blood is commenced
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