A Homologue ofN-Ethylmaleimide-sensitive Factor in the Malaria ParasitePlasmodium falciparum Is Exported and Localized in Vesicular Structures in the Cytoplasm of Infected Erythrocytes in the Brefeldin A-sensitive Pathway

Abstract

Plasmodium falciparum, a human malaria parasite, invades an erythrocyte during one stage of its life cycle. In an infected erythrocyte, the P. falciparum organism develops a membrane structure called the parasitophorus vacuolar membrane. The parasitophorus vacuolar membrane extends into the host cell cytoplasm and forms a complex membrane structure, thus called the tubovesicular membrane network (reviewed in Refs. 1-3). These membrane systems outside the P. falciparum cell are important for the transport of various nutrients such as glucose, phospholipids, and amino acids and for extrusion of antimalarial agents so as to maintain suitable circumstances for them (3-6). In addition to the formation of such intraerythrocytic membrane systems, P. falciparum cells also transport some proteins such as erythrocyte membrane protein-1 of P. falciparum (PfEMP1) 1 and PfEMP3 to the erythrocyte plasma membrane, which results in the formation of a knob-like structure on the surfaces of the infected erythrocytes. These proteins are responsible for protection against immunological attack and attachment of infected erythrocyte to endothelial cells, one of the crucial steps for cerebral malaria (1-3, 7-11). Importantly, the extraparasite protein transport process can not rely upon the endogenous transport machinery in the host cells, because mature erythrocytes are completely devoid of machinery for protein trafficking. Thus, the malaria parasite must transport proteins through the plasma membrane and the membrane structure in the cytoplasm of the host cells by means of their own mechanism, although the molecular pathway for the transport of proteins through the parasite plasma membrane is less understood.It has been shown that the transport of some proteins from malaria parasites is sensitive to BFA (12-16), which is a well known macrolide antibiotic produced by fungi that blocks eukaryotic protein trafficking processes, especially transport from the endoplasmic reticulum to the Golgi apparatus by inhibiting the activities of ADP-ribosylation factors and guanine nucleotide exchange factors (17). These results suggest that the transport pathway from the endoplasmic reticulum to the Golgi apparatus is involved in the targeting of parasite

Dissection of brefeldin A-sensitive and -insensitive steps in apicoplast protein targeting

“…Both of these findings also support the hypothesis that proteins do not need to traverse the Golgi to reach the apicoplast. In studies of P. falciparum, immunoelectron microscopy detected NSF1, a component of complexes that catalyze vesicular fusion, associated with membranes of the apicoplast (Hayashi et al, 2001). This observation is consistent with vesicular fusion and hence a GEF being required for ongoing protein import into the organelle.…”

Trafic protéique dans le globule rouge infecté parPlasmodium

“…COPI ne jouant aucun rôle dans le secteur externe de la voie de trafic, le trafic vésiculaire des protéines à travers le cytosol érythrocytaire serait donc unidirectionnel [15]. Le NSF (N-ethylmaleimide sensitive factor), qui fait partie du complexe de fusion/arrimage des vésicules chez les eucaryotes, participerait également au trafic intraérythrocytaire [24].…”

“…PfNSF VD, apicoplaste Composant des vésicules de fusion, probablement impliqué dans la biogenèse de la VD par fusion de vésicules, et rôle possible dans l'adressage des protéines à l'apicoplaste [24] pfSec31p RE Protéine COPII, trafic des protéines du RE vers le Golgi [23] Rab6…”

“…GTPase, rôle régulateur du trafic protéique [39] PfSec61a RE Probablement impliquée dans la translocation des peptides au cours de leur traduction à travers la membrane du RE [40] Pf COP RE, trans-Golgi Protéine COPI, impliquée dans le transport antérograde [15] Falcipaïnes et VD Protéases impliquées dans la dégradation de l'hémoglobine [41,42] plasmepsines HRP2 VD Impliquée dans la formation de l'hémozoïne et dans la détoxication des produits de dégradation de l'hémoglobine [38] PDH Apicoplaste Enzyme impliquée dans la conversion du pyruvate en acétyl-CoA (principal précurseur des acides gras) [43] Pf1-Cys-Prx Cytoplasme Rôle dans la détoxication des espèces réactives de l'oxygène parasitaire libérées notamment par le fer de l'hème de l'hémoglobine [43] PfTPx-2 Mitochondrie Protéine antioxydante probablement en relation avec la chaîne respiratoire [44] PfNSF Cytoplasme du GR, FM Impliquée dans le transport vésiculaire des protéines vers la membrane du GR [24] pfSec31p FM Protéine COPII, trafic des protéines à travers le cytoplasme du GR, impliquée dans le transport du PIEMP1 [23] Rab6…”

The Apicoplast: A Review of the Derived Plastid of Apicomplexan Parasites

“…If no continuity occurs between the ER and the apicoplast then vesicular traffic must be considered and recent data suggests that NSF (N-ethylmaleimidesensitive factor)-mediated vesicle docking does occur at the outer apicoplast membrane (Hayashi et al, 2001). What then directs vesicles to the apicoplast?…”