Plasmodium lipid rafts contain proteins implicated in vesicular trafficking and signalling as well as members of the PIR superfamily, potentially implicated in host immune system interactions.
Plasmodium parasites, the causal agents of malaria, dramatically modify the infected erythrocyte by exporting parasite proteins into one or multiple erythrocyte compartments, the cytoplasm and the plasma membrane or beyond. Despite advances in defining signals and specific cellular compartments implicated in protein trafficking in Plasmodium-infected erythrocytes, the contribution of lipid-mediated sorting to this cellular process has been poorly investigated. In this study, we examined the proteome of cholesterol-rich membrane microdomains or lipid rafts, purified from erythrocytes infected by the rodent parasite Plasmodium berghei. Besides structural proteins associated with invasive forms, we detected chaperones, proteins implicated in vesicular trafficking, membrane fusion events and signalling. Interestingly, the raft proteome of mixed P. berghei blood stages included proteins encoded by members of a large family (bir) of putative variant antigens potentially implicated in host immune system interactions and targeted to the surface of the host erythrocytes. The generation of transgenic parasites expressing BIR/GFP fusions confirmed the dynamic association of members of this protein family with membrane microdomains. Our results indicated that lipid rafts in Plasmodium-infected erythrocytes might constitute a route to sort and fold parasite proteins directed to various host cell compartments including the cell surface.
Di Girolamo
Francesco
F
Dipartimento di Malattie Infettive Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Roma, Italy.
Raggi
Carla
C
Birago
Cecilia
C
Pizzi
Elisabetta
E
Lalle
Marco
M
Picci
Leonardo
L
Pace
Tomasino
T
Bachi
Angela
A
de Jong
Joke
J
Janse
Chris J
CJ
Waters
Andrew P
AP
Sargiacomo
Massimo
M
Ponzi
Marta
M
D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology*; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006790:Host-Parasite Interactions; D006801:Humans; D008018:Life Cycle Stages; D021962:Membrane Microdomains / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D010961:Plasmodium / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010962:Plasmodium berghei / Q000235:genetics / Q000254:growth & development / Q000469:parasitology; D021381:Protein Transport; D040901:Proteomics / Q000379:methods; D015800:Protozoan Proteins / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction; D022161:Transport Vesicles / Q000378:metabolism*; D014357:Trypsin / Q000494:pharmacology
D000941:Antigens; D015800:Protozoan Proteins; D014357:Trypsin