The ETRAMP Family Member SEP2 Is Expressed throughout Plasmodium berghei Life Cycle and Is Released during Sporozoite Gliding Motility

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.

SSP3 Is a Novel Plasmodium yoelii Sporozoite Surface Protein with a Role in Gliding Motility

“…The most studied ones are CSP and TRAP, both of which are important for gliding motility, salivary gland infection, and recognition and invasion of hepatocytes (39). Other sporozoite surface proteins include AMA-1, which relocates from micronemes to the surface upon sporozoite activation but is dispensable for hepatocyte infection (46,47), a secreted phospholipase involved in cell traversal (48), rhomboid protease 4, which cleaves TRAP (36), sporozoite invasion-associated protein 1 with a role in sporozoite motility (49,50), and a few surface antigens with unknown function (51)(52)(53)(54).…”

Evaluation of antibody responses to the early transcribed membrane protein family in Plasmodium vivax

“…Interestingly, most ETRAMPs are expressed in stage-specific expression patterns during the parasite life cycle, and they mostly localize to the parasitophorous vacuole membrane (PVM), which spatially separates the parasite from the cytosol of erythrocytes in infected RBCs and mediates the free passage of molecules, probably through membranous pores such as the Plasmodium translocon for exported proteins (PTEX) and exported protein 1 (EXP1) [18–22]. On the other hand, the P. berghei ETRAMP family member small exported protein 2 (SEP2), localizes to membranous compartments of the ookinete and is released during gliding motility in the sporozoite, indicating that the protein family is involved in not only blood stage but also sexual stage [23].…”

Interactions ofPlasmodium falciparumETRAMP14.1 with PfEMP1, translocon components and other ETRAMP members at the interface of host-parasite

“…However, many studies have proposed functions for ETRAMPs based on their location in PVM such as, junction formation between tubovesicular network (TVN) and the RBC membrane to obtain nutrients, vesicular transport processes at PVM or stabilizing PVM 10 . A P. berghei ETRAMP family member, SEP2 which is abundantly expressed in gametocytes as well as in mosquito and liver stages is important in gliding motility of sporozoites thereby accounting as a promising transmission-blocking candidate 12 . Furthermore, P.yoelii and P. berghei UIS genes, UIS4 and UIS3, specifically expressed in sporozoites, are ETRAMP orthologs.…”