The mature-parasite-infected erythrocyte surface antigen (MESA) of Plasmodium falciparum associates with the erythrocyte membrane skeletal protein, band 4.1

Abstract 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.

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Role of the Plasmodium falciparum mature-parasite-infected erythrocyte surface antigen (MESA/PfEMP-2) in malarial infection of erythrocytes

Blood ◽

10.1182/blood.v86.8.3196.bloodjournal8683196 ◽

1995 ◽

Vol 86 (8) ◽

pp. 3196-3204

Author(s):

C Magowan ◽

RL Coppel ◽

AO Lau ◽

MM Moronne ◽

G Tchernia ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Erythrocyte Membrane ◽

Surface Antigen ◽

Infected Erythrocyte ◽

Spontaneous Mutant ◽

Protein 4.1 ◽

Erythrocyte Surface ◽

Skeletal Protein ◽

Parasite Viability

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.

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The ring-infected erythrocyte surface antigen of Plasmodium falciparum associates with spectrin in the erythrocyte membrane

Molecular and Biochemical Parasitology ◽

10.1016/0166-6851(91)90207-m ◽

1991 ◽

Vol 46 (1) ◽

pp. 137-147 ◽

Cited By ~ 83

Author(s):

Michael Foley ◽

Leann Tilley ◽

William H. Sawyer ◽

Robin F. Anders

Keyword(s):

Plasmodium Falciparum ◽

Erythrocyte Membrane ◽

Surface Antigen ◽

Infected Erythrocyte ◽

Erythrocyte Surface

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Parasitized Erythrocyte Membrane Antigens of Plasmodium brasilianum: Relationships with the Ring-Infected Erythrocyte Surface Antigen of Plasmodium falciparum

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.1995.53.618 ◽

1995 ◽

Vol 53 (6) ◽

pp. 618-623 ◽

Cited By ~ 1

Author(s):

Alexander J. Sulzer ◽

Raul A. Cantella ◽

William P. Carney ◽

William E. Collins

Keyword(s):

Plasmodium Falciparum ◽

Erythrocyte Membrane ◽

Surface Antigen ◽

Infected Erythrocyte ◽

Erythrocyte Surface ◽

Membrane Antigens ◽

Plasmodium Brasilianum

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Expression of the RESA gene in Plasmodium falciparum isolate FCR3 is prevented by a subtelomeric deletion

Molecular and Cellular Biology ◽

10.1128/mcb.9.8.3584-3587.1989 ◽

1989 ◽

Vol 9 (8) ◽

pp. 3584-3587

Author(s):

R Cappai ◽

M R van Schravendijk ◽

R F Anders ◽

M G Peterson ◽

L M Thomas ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Surface Antigen ◽

Infected Erythrocyte ◽

Falciparum Isolate ◽

Erythrocyte Surface ◽

Subtelomeric Deletion

We show here that the Plasmodium falciparum isolate FCR3 does not express the ring-infected erythrocyte surface antigen (RESA). This is because the 5' end of the RESA gene has been inverted and partly deleted and a telomere has been added to it. We propose a model to explain these events.

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The ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum stabilizes spectrin tetramers and suppresses further invasion

Blood ◽

10.1182/blood-2007-02-076919 ◽

2007 ◽

Vol 110 (3) ◽

pp. 1036-1042 ◽

Cited By ~ 90

Author(s):

Xinhong Pei ◽

Xinhua Guo ◽

Ross Coppel ◽

Souvik Bhattacharjee ◽

Kasturi Haldar ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Surface Antigen ◽

Infected Erythrocyte ◽

Host Cell Membrane ◽

Acid Fragment ◽

Erythrocyte Surface ◽

Parasite Plasmodium Falciparum ◽

Functional Consequences ◽

Self Association ◽

Resistance To Invasion

AbstractThe malaria parasite Plasmodium falciparum releases the ring-infected erythrocyte surface antigen (RESA) inside the red cell on entry. The protein migrates to the host cell membrane, where it binds to spectrin, but neither the nature of the interaction nor its functional consequences have previously been defined. Here, we identify the binding motifs involved in the interaction and describe a possible function. We have found that spectrin binds to a 108–amino acid fragment (residues 663-770) of RESA, and that this RESA fragment binds to repeat 16 of the β-chain, close to the labile dimer-dimer self-association site. We further show that the RESA fragment stabilizes the spectrin tetramer against dissociation into its constituent dimers, both in situ and in solution. This is accompanied by enhanced resistance of the cell to both mechanical and thermal degradation. Resealed erythrocytes containing RESA663-770 display resistance to invasion by merozoites of P falciparum. We infer that the evolutionary advantage of RESA to the parasite lies in its ability to prevent invasion of cells that are already host to a developing parasite, as well as possibly to guard the cell against thermal damage at the elevated body temperatures prevailing in febrile crises.

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