Role of the Plasmodium falciparum mature-parasite-infected erythrocyte surface antigen (MESA/PfEMP-2) in malarial infection of erythrocytes.
During intraerythrocytic growth of Plasmodium falciparum, several parasite proteins are transported from the parasite to the erythrocyte membrane, where they bind to membrane skeletal proteins. Mature-parasite-infected erythrocyte surface antigen (MESA) has previously been shown to associate with host erythrocyte membrane skeletal protein 4.1. Using a spontaneous mutant of P falciparum that has lost the ability to synthesize MESA and 4.1-deficient erythrocytes, we examined growth of MESA(+) and MESA(-) parasites in normal and 4.1-deficient erythrocytes. Viability of MESA(+) parasites was reduced in 4.1-deficient erythrocytes as compared with that for normal erythrocytes, but MESA(-) parasites grew equally well in 4.1-deficient and normal erythrocytes. Cytoadherence of MESA(+)- and MESA (-)-parasitized normal and 4.1-deficient erythrocytes to C32 melanoma cells was similar, indicating that neither protein 4.1 nor MESA plays a major role in cytoadherence of infected erythrocytes. Localization of MESA in normal and 4.1-deficient erythrocytes was examined by confocal microscopy. MESA was diffusely distributed in the cytosol of 4.1-deficient erythrocytes but was membrane-associated in normal erythrocytes. These findings suggest that MESA binding to protein 4.1 plays a major role in intraerythrocytic parasite viability.
Magowan
C
C
Life Sciences Division, Lawrence Berkeley Laboratory, Berkeley, CA, USA.
Coppel
R L
RL
Lau
A O
AO
Moronne
M M
MM
Tchernia
G
G
Mohandas
N
N
D000818:Animals; D000953:Antigens, Protozoan / Q000502:physiology*; D002448:Cell Adhesion; D003598:Cytoskeletal Proteins; D004912:Erythrocytes / Q000469:parasitology*; D006790:Host-Parasite Interactions; D016778:Malaria, Falciparum / Q000097:blood*; D008545:Melanoma / Q000473:pathology; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D018613:Microscopy, Confocal; D009479:Neuropeptides; D010455:Peptides / Q000502:physiology; D010963:Plasmodium falciparum / Q000276:immunology / Q000502:physiology*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000502:physiology*; D011817:Rabbits; D014407:Tumor Cells, Cultured
D000953:Antigens, Protozoan; D003598:Cytoskeletal Proteins; C079081:MESA protein, Plasmodium falciparum; D008565:Membrane Proteins; D009479:Neuropeptides; D010455:Peptides; D015800:Protozoan Proteins; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1; C042968:knob protein, Plasmodium falciparum