ArticleThe Journal of biological chemistry2007
Two functionally divergent UDP-Gal nucleotide sugar transporters participate in phosphoglycan synthesis in Leishmania major.
Article in The Journal of biological chemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 64 citations in OpenAlex.
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- NLRP12-expressing dendritic cells mediate both dissemination of infection and adaptive immune responses in visceral leishmaniasis.iScience · 2023Article
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- Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose TransporterMicrobiology spectrum · 2022Article
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- A broadly active fucosyltransferase LmjFUT1 whose mitochondrial localization and activity are essential in parasiticProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Establishment, optimisation and quantitation of a bioluminescent murine infection model of visceral leishmaniasis for systematic vaccine screening.Scientific reports · 2020Article
- Proteins involved in the biosynthesis of lipophosphoglycan in Leishmania: a comparative genomic and evolutionary analysis.Parasites & vectors · 2020Article
- Transcriptional and genomic parallels between the monoxenous parasite Herpetomonas muscarum and Leishmania.PLoS genetics · 2019Article
- Gateway to the Golgi: molecular mechanisms of nucleotide sugar transporters.Current opinion in structural biology · 2019Review
- Whole genome sequencing of experimental hybrids supports meiosis-like sexual recombination in Leishmania.PLoS genetics · 2019Article
- Development of Thiophene Compounds as Potent Chemotherapies for the Treatment of Cutaneous Leishmaniasis Caused byMolecules (Basel, Switzerland) · 2018Article
- Genetic metabolic complementation establishes a requirement for GDP-fucose inThe Journal of biological chemistry · 2017Article
- Identification of a Golgi-localized UDP-N-acetylglucosamine transporter in Trypanosoma cruzi.BMC microbiology · 2015Article
- Evaluation of α,β-unsaturated ketones as antileishmanial agents.Antimicrobial agents and chemotherapy · 2015Article
- Golgi-located NTPDase1 of Leishmania major is required for lipophosphoglycan elongation and normal lesion development whereas secreted NTPDase2 is dispensable for virulence.PLoS neglected tropical diseases · 2014Article
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5 authors at 2 institutions in 1 country.
Funding
Abstract
In the protozoan parasite Leishmania, abundant surface and secreted molecules, such as lipophosphoglycan (LPG) and proteophosphoglycans (PPGs), contain extensive galactose in the form of phosphoglycans (PGs) based on (Gal-Man-PO(4)) repeating units. PGs are synthesized in the parasite Golgi apparatus and require transport of cytoplasmic nucleotide sugar precursors to the Golgi lumen by nucleotide sugar transporters (NSTs). GDP-Man transport is mediated by the LPG2 gene product, and here we focused on transporters for UDP-Gal. Data base mining revealed 12 candidate NST genes in the L. major genome, including LPG2 as well as a candidate endoplasmic reticulum UDP-glucose transporter (HUT1L) and several pseudogenes. Gene knock-out studies established that two genes (LPG5A and LPG5B) encoded UDP-Gal NSTs. Although the single lpg5A(-) and lpg5B(-) mutants produced PGs, an lpg5A(-)/5B(-) double mutant was completely deficient. PG synthesis was restored in the lpg5A(-)/5B(-) mutant by heterologous expression of the human UDP-Gal transporter, and heterologous expression of LPG5A and LPG5B rescued the glycosylation defects of the mammalian Lec8 mutant, which is deficient in UDP-Gal uptake. Interestingly, the LPG5A and LPG5B functions overlap but are not equivalent, since the lpg5A(-) mutant showed a partial defect in LPG but not PPG phosphoglycosylation, whereas the lpg5B(-) mutant showed a partial defect in PPG but not LPG phosphoglycosylation. Identification of these key NSTs in Leishmania will facilitate the dissection of glycoconjugate synthesis and its role(s) in the parasite life cycle and further our understanding of NSTs generally.
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