Protein phosphatase 1, a Plasmodium falciparum essential enzyme, is exported to the host cell and implicated in the release of infectious merozoites.
The malarial parasite Plasmodium falciparum transposes a Golgi-like compartment, referred to as Maurer's clefts, into the cytoplasm of its host cell, the erythrocyte, and delivering parasite molecules to the host cell surface. We report here a novel role of the Maurer's clefts implicating a parasite protein phosphatase 1 (PP1) and related to the phosphorylation status of P. falciparum skeleton-binding protein 1 (PfSBP1), a trans-membrane protein of the clefts interacting with the host cell membrane via its carboxy-terminal domain. Based on co-immunoprecipitation and inhibition studies, we show that the parasite PP1 type phosphatase modulates the phosphorylation status of the amino-terminal domain of PfSBP1 in the lumen of Maurer's clefts. Importantly, the addition of a PP1 inhibitor, calyculin A, to late schizonts results in the hyperphosphorylation of PfSBP1 and prevents parasite release from the host cell. We propose that the hyperphosphorylation of PfSBP1 interferes with the release of merozoites, the invasive blood stage of the parasite, by increasing the red cell membrane stability. Moreover, the parasite PP1 phosphatase is the first enzyme essential for the parasite development detected in the Maurer's clefts.
Unité de Biologie des Interactions Hôte-Parasite, CNRS URA 2581, France.
Thierry
T
Blisnick
Laetitia
L
Vincensini
Gamou
G
Fall
Catherine
C
Braun-Breton
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D006056:Golgi Apparatus / Q000378:metabolism; D066298:In Vitro Techniques; D008387:Marine Toxins; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008969:Molecular Sequence Data; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000201:enzymology / Q000502:physiology*; D054645:Protein Phosphatase 1; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
D002352:Carrier Proteins; D008387:Marine Toxins; D008565:Membrane Proteins; D010080:Oxazoles; C417763:Pfsbp1 protein, Plasmodium falciparum; D015800:Protozoan Proteins; C059041:calyculin A; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1