In eukaryotic cells, transport of macromolecules depends on bi-directional movement of vesicles between compartments. Both the formation of transport vesicles at the donor compartment and targeting/docking of these vesicles containing the cargo at the acceptor compartment are controlled by specific GTPases and involve a complex network of many regulatory molecules as well as mechanical components. From each organelle proteins and lipids (cargo) are selectively packaged into vesicles that specifically recognize the acceptor compartment, fuse with it and deliver the cargo. The cargo destined to leave the donor compartment is incorporated into vesicles via an interaction with cytoplasmic proteins, which assemble to form a coat. Coat assembly promotes a change in the shape of the donor membrane compartment and induces formation of transport vesicles. Targeting/docking and fusion of vesicles at the acceptor membranes require interaction with actin and microtubule cytoskeleton, recruitment of cytosolic docking complexes and specific recognition between integral membrane proteins known as v-SNARE and t-SNARE.

“….With the exception of the sporozoite and merozoite, all developmental stages of malaria parasite are intracellular. The presence of the intracellular parasite makes the host erythrocyte a target for destruction by spleen. To overcome this, the parasite modifies the surface properties of erythrocyte by exporting proteins to the surface of the host cells. This is remarkable because within the erythrocyte the parasite is surrounded by its own plasma membrane, the parasitophorous vacuole, the parasitophorous vacuole membrane (PVM) and the erythrocyte cytoplasm, and is topologically a long way from the erythrocyte membrane. Furthermore, the mature erythrocyte has no lipid or protein trafficking machinery. Nonetheless, the parasite exports proteins that change the surface properties, permeability and transport characteristics of host erythrocyte membrane, resulting in increased uptake of the additional nutrients required by the parasite…” -Langsley and others.

Current evidences suggest that both a classical ER and Golgi mediated pathway and unusual secretory pathway exists in Plasmodium. Elements of the classical vesicle-mediated secretory pathway for the export of proteins are present within the parasite cytoplasm. These include homologues of ER calcium binding protein, ER molecular chaperone Pfgrp, a number of Rab GTPases, a homologue of the KDEL binding protein PfERD2 and an ARFGTPase. Homologue of Sar1p has been located in a defined compartment adjacent to the parasite periphery and associated with vesicular structures within the erythrocyte cytosol. Recently Trelka and his colleagues presented evidence for vesicle mediated trafficking Plasmodium proteins to the cytosol and surface membrane of infected erythrocytes.

We are studying the structural biology of the protein trafficking machinery of the malaria parasite.

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