ArticleEukaryotic cell2007
De novo sphingolipid synthesis is essential for viability, but not for transport of glycosylphosphatidylinositol-anchored proteins, in African trypanosomes.
Article in Eukaryotic cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
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- The lipidome ofFrontiers in cellular and infection microbiology · 2022Article
- Blocking variant surface glycoprotein synthesis alters endoplasmic reticulum exit sites/Golgi homeostasis in Trypanosoma brucei.Traffic (Copenhagen, Denmark) · 2018Article
- Everybody needs sphingolipids, right! Mining for new drug targets in protozoan sphingolipid biosynthesis.Parasitology · 2018Review
- Comparative sphingolipidomics of disease-causing trypanosomatids reveal unique lifecycle- and taxonomy-specific lipid chemistries.Scientific reports · 2017Article
- Controlling transferrin receptor trafficking with GPI-valence in bloodstream stage African trypanosomes.PLoS pathogens · 2017Article
- Identification and Characterization of FTY720 for the Treatment of Human African Trypanosomiasis.Antimicrobial agents and chemotherapy · 2015Article
- Localization of serum resistance-associated protein in Trypanosoma brucei rhodesiense and transgenic Trypanosoma brucei brucei.Cellular microbiology · 2015Article
- Lipid synthesis in protozoan parasites: a comparison between kinetoplastids and apicomplexans.Progress in lipid research · 2013Review
- Glycosylphosphatidylinositol anchors regulate glycosphingolipid levels.Journal of lipid research · 2012Article
- Form and function in the trypanosomal secretory pathway.Current opinion in microbiology · 2012Review
- Symmetrical choline-derived dications display strong anti-kinetoplastid activity.The Journal of antimicrobial chemotherapy · 2011Article
- The Sphingolipid Biosynthetic Pathway Is a Potential Target for Chemotherapy against Chagas Disease.Enzyme research · 2011Article
- Lipid metabolism in Trypanosoma brucei.Molecular and biochemical parasitology · 2010Review
- Lipidomic analysis of bloodstream and procyclic form Trypanosoma brucei.Parasitology · 2010Review
- Trypanosoma brucei: trypanosome-specific endoplasmic reticulum proteins involved in variant surface glycoprotein expression.Experimental parasitology · 2010Article
- The essential neutral sphingomyelinase is involved in the trafficking of the variant surface glycoprotein in the bloodstream form of Trypanosoma brucei.Molecular microbiology · 2010Article
- Phospholipid and sphingolipid metabolism in Leishmania.Molecular and biochemical parasitology · 2010Review
- Sphingolipids in parasitic protozoa.Advances in experimental medicine and biology · 2010Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
De novo sphingolipid synthesis is required for the exit of glycosylphosphatidylinositol (GPI)-anchored membrane proteins from the endoplasmic reticulum in yeast. Using a pharmacological approach, we test the generality of this phenomenon by analyzing the transport of GPI-anchored cargo in widely divergent eukaryotic systems represented by African trypanosomes and HeLa cells. Myriocin, which blocks the first step of sphingolipid synthesis (serine + palmitate --> 3-ketodihydrosphingosine), inhibited the growth of cultured bloodstream parasites, and growth was rescued with exogenous 3-ketodihydrosphingosine. Myriocin also blocked metabolic incorporation of [3H]serine into base-resistant sphingolipids. Biochemical analyses indicate that the radiolabeled lipids are not sphingomyelin or inositol phosphorylceramide, suggesting that bloodstream trypanosomes synthesize novel sphingolipids. Inhibition of de novo sphingolipid synthesis with myriocin had no adverse effect on either general secretory trafficking or GPI-dependent trafficking in trypanosomes, and similar results were obtained with HeLa cells. A mild effect on endocytosis was seen for bloodstream trypanosomes after prolonged incubation with myriocin. These results indicate that de novo synthesis of sphingolipids is not a general requirement for secretory trafficking in eukaryotic cells. However, in contrast to the closely related kinetoplastid Leishmania major, de novo sphingolipid synthesis is essential for the viability of bloodstream-stage African trypanosomes.
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