Traffic to the malaria parasite food vacuole: a novel pathway involving a phosphatidylinositol 3-phosphate-binding protein.
Phosphatidylinositol 3-phosphate (PI3P) is a key ligand for recruitment of endosomal regulatory proteins in higher eukaryotes. Subsets of these endosomal proteins possess a highly selective PI3P binding zinc finger motif belonging to the FYVE domain family. We have identified a single FYVE domain-containing protein in Plasmodium falciparum which we term FCP. Expression and mutagenesis studies demonstrate that key residues are involved in specific binding to PI3P. In contrast to FYVE proteins in other organisms, endogenous FCP localizes to a lysosomal compartment, the malaria parasite food vacuole (FV), rather than to cytoplasmic endocytic organelles. Transfections of deletion mutants further indicate that FCP is essential for trophozoite and FV maturation and that it traffics to the FV via a novel constitutive cytoplasmic to vacuole targeting pathway. This newly discovered pathway excludes the secretory pathway and is directed by a C-terminal 44-amino acid peptide domain. We conclude that an FYVE protein that might be expected to participate in vesicle targeting in the parasite cytosol instead has a vital and functional role in the malaria parasite FV.
McIntosh
Michael T
MT
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA. michael.mcintosh@yale.edu
Vaid
Ankush
A
Hosgood
H Dean
HD
Vijay
Justin
J
Bhattacharya
Anindita
A
Sahani
Mayurbhai H
MH
Baevova
Pavlina
P
Joiner
Keith A
KA
Sharma
Pushkar
P
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D017124:Conserved Sequence; D020285:Cryoelectron Microscopy; D017353:Gene Deletion; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000166:cytology* / Q000378:metabolism*; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014617:Vacuoles / Q000378:metabolism*
D018129:Phosphatidylinositol Phosphates; D015800:Protozoan Proteins; C055525:phosphatidylinositol 3-phosphate