The Maurer's cleft protein MAHRP1 is essential for trafficking of PfEMP1 to the surface of Plasmodium falciparum-infected erythrocytes.
During the intra-erythrocytic development of Plasmodium falciparum, the parasite modifies the host cell surface by exporting proteins that interact with or insert into the erythrocyte membrane. These proteins include the principal mediator of cytoadherence, P. falciparum erythrocyte membrane protein 1 (PfEMP1). To implement these changes, the parasite establishes a protein-trafficking system beyond its confines. Membrane-bound structures called Maurer's clefts are intermediate trafficking compartments for proteins destined for the host cell membrane. We disrupted the gene for the membrane-associated histidine-rich protein 1 (MAHRP1). MAHRP1 is not essential for parasite viability or Maurer's cleft formation; however, in its absence, these organelles become disorganized in permeabilized cells. Maurer's cleft-resident proteins and transit cargo are exported normally in the absence of MAHRP1; however, the virulence determinant, PfEMP1, accumulates within the parasite, is depleted from the Maurer's clefts and is not presented at the red blood cell surface. Complementation of the mutant parasites with mahrp1 led to the reappearance of PfEMP1 on the infected red blood cell surface, and binding studies show that PfEMP1-mediated binding to CD36 is restored. These data suggest an important role of MAHRP1 in the translocation of PfEMP1 from the parasite to the host cell membrane.
Spycher
Cornelia
C
Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Socinstrasse 57, CH 4002 Basel, Switzerland.
Rug
Melanie
M
Pachlatko
Esther
E
Hanssen
Eric
E
Ferguson
David
D
Cowman
Alan F
AF
Tilley
Leann
L
Beck
Hans-Peter
HP
D000818:Animals; D000953:Antigens, Protozoan / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology* / Q000648:ultrastructure; D008565:Membrane Proteins; D010963:Plasmodium falciparum / Q000378:metabolism* / Q000502:physiology; D021381:Protein Transport / Q000235:genetics / Q000502:physiology*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D002352:Carrier Proteins; C478484:MAHRP-1 protein, Plasmodium falciparum; D008565:Membrane Proteins; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum