ArticleThe Journal of biological chemistry2013
Trypanosoma brucei vacuolar transporter chaperone 4 (TbVtc4) is an acidocalcisome polyphosphate kinase required for in vivo infection.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 84 citations in OpenAlex.
- Novel binding partners of the Vacuolar Transporter Chaperone (VTC) complex in Acidocalcisomes of Leishmania tarentolae.PLoS neglected tropical diseases · 2026Article
- Article
- Acidocalcisome-like vacuoles constitute a feedback-controlled phosphate buffering system for the cytosol.eLife · 2025Article
- Impacts of Cipargamin on NaMembranes · 2025Article
- Article
- Review
- A fusion protein of polyphosphate kinase 1 (PPK1) and a Nudix hydrolase is involved in inorganic polyphosphate accumulation in the unicellular red alga Cyanidioschyzon merolae.Plant molecular biology · 2024Article
- The Protein Scaffolding Functions of Polyphosphate.Journal of molecular biology · 2024Review
- Advances in the cellular biology, biochemistry, and molecular biology of acidocalcisomes.Microbiology and molecular biology reviews : MMBR · 2024Review
- Plasmodium falciparum utilizes pyrophosphate to fuel an essential proton pump in the ring stage and the transition to trophozoite stage.PLoS pathogens · 2023Article
- Article
- How much (ATP) does it cost to build a trypanosome? A theoretical study on the quantity of ATP needed to maintain and duplicate a bloodstream-form Trypanosoma brucei cell.PLoS pathogens · 2023Article
- Cryo-EM structure of the polyphosphate polymerase VTC reveals coupling of polymer synthesis to membrane transit.The EMBO journal · 2023Article
- A spatially resolved elemental nanodomain organization within acidocalcisomes inProceedings of the National Academy of Sciences of the United States of America · 2023Article
- New insights into the role of acidocalcisomes in trypanosomatids.The Journal of eukaryotic microbiology · 2022Review
- MICU1 and MICU2 potentiation of CaCell calcium · 2022Article
- Dictyostelium discoideum cells retain nutrients when the cells are about to outgrow their food source.Journal of cell science · 2022Article
- Lessons from protozoans: Phosphate sensing and polyphosphate storage in fungi.PLoS pathogens · 2022Article
- Biomimetic Polyphosphate Materials: Toward Application in Regenerative Medicine.Progress in molecular and subcellular biology · 2022Article
- Trypanosoma cruzi Letm1 is involved in mitochondrial CaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Polyphosphate (polyP) is an anionic polymer of orthophosphate groups linked by high energy bonds that typically accumulates in acidic, calcium-rich organelles known as acidocalcisomes. PolyP synthesis in eukaryotes was unclear until it was demonstrated that the protein named Vtc4p (vacuolar transporter chaperone 4) is a long chain polyP kinase that localizes to the yeast vacuole. Here, we report that TbVtc4 (Vtc4 ortholog of Trypanosoma brucei) encodes, in contrast, a short chain polyP kinase that localizes to acidocalcisomes. The subcellular localization of TbVtc4 was demonstrated by fluorescence and electron microscopy of cell lines expressing TbVtc4 in its endogenous locus fused to an epitope tag and by purified polyclonal antibodies against TbVtc4. Recombinant TbVtc4 was expressed in bacteria, and polyP kinase activity was assayed in vitro. The in vitro growth of conditional knock-out bloodstream form trypanosomes (TbVtc4-KO) was significantly affected relative to the parental cell line. This mutant had reduced polyP kinase activity and short chain polyP content and was considerably less virulent in mice. The wild-type phenotype was recovered when an ectopic copy of the TbVtc4 gene was expressed in the presence of doxycycline. The mutant also exhibited a defect in volume recovery under osmotic stress conditions in vitro, underscoring the relevance of polyP in osmoregulation.
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