Protein Trafficking to Apical Organelles of Malaria Parasites – Building an Invasion Machine

Abstract

Malaria is caused by four species of apicomplexan protozoa belonging to the genus Plasmodium. These parasites possess a specialized collection of secretory organelles called rhoptries, micronemes and dense granules (DGs) that in part facilitate invasion of host cells. The mechanism by which the parasite traffics proteins to these organelles as well as regulates their secretion has important implications for understanding the invasion process and may lead to development of novel intervention strategies. In this review, we focus on emerging data about trafficking signals, mechanisms of biogenesis and secretion. At least some of these are conserved in higher eukaryotes, suggesting that rhoptries, micronemes and DGs are related to organelles such as secretory lysosomes that are well known to mainstream cell biologists.

An essential dual-function complex mediates erythrocyte invasion and channel-mediated nutrient uptake in malaria parasites

“…As GlcN was without effect in untransfected parasites (Figure 3—figure supplement 1A), these findings indicate that these proteins require interactions with their cognate partners for successful transfer to the next erythrocyte at the time of invasion. They argue against transfer by simple entrapment of rhoptry proteins in the nascent parasitophorous vacuole during invasion (Kats et al, 2008).

10.7554/eLife.23485.005Figure 3.Transfer of intact complexes to new host cells and no role for RhopH proteins in vacuolar function.( A ) Schematic showing timeline for GlcN exposure, rhoph gene expression, and subsequent harvest of trophozoite-infected cells.

…”

Plasmodium rhoptry proteins: why order is important

“…In the case of Plasmodium, Rabs, SNAREs, and AP1 have been identified in the genome [24], but the majority of known rhoptry proteins are soluble, and thus the mechanism by which rhoptry cargo in Golgi-derived trafficking vesicles engage with the cytoplasmic trafficking machinery is still very much a black box. In fact, only a limited number of studies with a focus on rhoptry protein trafficking have been performed in Plasmodium.…”

Comparative Genomic Analysis of Multi-Subunit Tethering Complexes Demonstrates an Ancient Pan-Eukaryotic Complement and Sculpting in Apicomplexa

“…Additionally, soluble rhoptry and microneme proteins may also possess multiple independent targeting signals [26], and other pathways have been proposed [27]. The biogenesis and function of these organelles depends on the timely and accurate delivery of protein and lipid components, and although the membrane-trafficking system is clearly involved, the mechanisms and critical components underpinning such processes remain largely unknown (reviewed in [28]).…”