Secretion of an acid phosphatase provides a possible mechanism to acquire host nutrients by Plasmodium falciparum.
As an intracellular proliferating parasite, Plasmodium falciparum exploits the human host to acquire nutrients. However, nutrients such as nucleotides and cofactors are mostly phosphorylated in the host cell cytosol and thus have to be dephosphorylated in order to be taken up by the parasite. Here we report the functional characterization of a unique secreted phosphatase in P. falciparum, which is expressed throughout the developmental stages in the red blood cell. We show that this enzyme, formerly described as anchoring glideosome-associated protein 50 (GAP50), reveals a broad substrate profile with preference for di- and triphosphates at pH 5-7. Bioinformatic studies of the protein sequence identified an N-terminal signal anchor (SA) as well as a C-terminal transmembrane domain. By means of live microscopy of parasites transfected with GFP-fusions of this secreted acid phosphatase (PfSAP), we demonstrate that PfSAP enters the secretory pathway en route to the parasite periphery - mediated by SA - and is subsequently engulfed into the food vacuole. We corroborate this with independent data where acid phosphatase activity is visualized in close proximity to hemozoin. The biochemical as well as the trafficking results support the proposed role of PfSAP in the acquisition of host nutrients by dephosphorylation.
Müller
Ingrid B
IB
Bernhard Nocht Institute for Tropical Medicine, Department of Biochemistry, Hamburg, Germany. ibmueller@bni-hamburg.de
Knöckel
Julia
J
Eschbach
Marie-Luise
ML
Bergmann
Bärbel
B
Walter
Rolf D
RD
Wrenger
Carsten
C
D000135:Acid Phosphatase / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010710:Phosphates / Q000378:metabolism; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D016415:Sequence Alignment; D013379:Substrate Specificity
D008565:Membrane Proteins; D010710:Phosphates; C509919:glideosome-associated protein 50, Plasmodium falciparum; D000135:Acid Phosphatase