Traffic to the malaria parasite food vacuole: A novel pathway involving a phosphatidylinositol 3-phosphate-binding protein

Michael T. McIntosh, Ankush Vaid, Howard D. Hosgood, Justin Vijay, Anindita Bhattacharya, Mayurbhai H. Sahani, Pavlina Baevova, Keith A. Joiner, Pushkar Sharma

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)11499-11508
Number of pages10
JournalJournal of Biological Chemistry
Volume282
Issue number15
DOIs
StatePublished - Apr 13 2007
Externally publishedYes

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Phosphate-Binding Proteins
Vacuoles
Malaria
Parasites
Food
Proteins
Trophozoites
Mutagenesis
Secretory Pathway
Zinc Fingers
Plasmodium falciparum
Eukaryota
Organelles
Cytosol
Transfection
Zinc
phosphatidylinositol 3-phosphate
Ligands
Amino Acids
Peptides

ASJC Scopus subject areas

  • Biochemistry

Cite this

Traffic to the malaria parasite food vacuole : A novel pathway involving a phosphatidylinositol 3-phosphate-binding protein. / McIntosh, Michael T.; Vaid, Ankush; Hosgood, Howard D.; Vijay, Justin; Bhattacharya, Anindita; Sahani, Mayurbhai H.; Baevova, Pavlina; Joiner, Keith A.; Sharma, Pushkar.

In: Journal of Biological Chemistry, Vol. 282, No. 15, 13.04.2007, p. 11499-11508.

Research output: Contribution to journalArticle

McIntosh, MT, Vaid, A, Hosgood, HD, Vijay, J, Bhattacharya, A, Sahani, MH, Baevova, P, Joiner, KA & Sharma, P 2007, 'Traffic to the malaria parasite food vacuole: A novel pathway involving a phosphatidylinositol 3-phosphate-binding protein', Journal of Biological Chemistry, vol. 282, no. 15, pp. 11499-11508. https://doi.org/10.1074/jbc.M610974200
McIntosh, Michael T. ; Vaid, Ankush ; Hosgood, Howard D. ; Vijay, Justin ; Bhattacharya, Anindita ; Sahani, Mayurbhai H. ; Baevova, Pavlina ; Joiner, Keith A. ; Sharma, Pushkar. / Traffic to the malaria parasite food vacuole : A novel pathway involving a phosphatidylinositol 3-phosphate-binding protein. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 15. pp. 11499-11508.
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