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Article: De novo sphingolipid synthesis is essential for viability, but not for transport of glycosylphosphatidylinositol-anchored proteins, in African trypanosomes

TitleDe novo sphingolipid synthesis is essential for viability, but not for transport of glycosylphosphatidylinositol-anchored proteins, in African trypanosomes
Authors
Issue Date2007
Citation
Eukaryotic Cell, 2007, v. 6 n. 3, p. 454-464 How to Cite?
AbstractDe 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, whicli 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. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Persistent Identifierhttp://hdl.handle.net/10722/188676
ISSN
2015 Impact Factor: 2.946
2015 SCImago Journal Rankings: 1.918
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorSutterwala, SSen_US
dc.contributor.authorCreswell, CHen_US
dc.contributor.authorSanyal, Sen_US
dc.contributor.authorMenon, AKen_US
dc.contributor.authorBangs, JDen_US
dc.date.accessioned2013-09-03T04:12:43Z-
dc.date.available2013-09-03T04:12:43Z-
dc.date.issued2007en_US
dc.identifier.citationEukaryotic Cell, 2007, v. 6 n. 3, p. 454-464en_US
dc.identifier.issn1535-9778en_US
dc.identifier.urihttp://hdl.handle.net/10722/188676-
dc.description.abstractDe 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, whicli 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. Copyright © 2007, American Society for Microbiology. All Rights Reserved.en_US
dc.languageengen_US
dc.relation.ispartofEukaryotic Cellen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCell Culture Techniquesen_US
dc.subject.meshCell Cycle Proteins - Metabolismen_US
dc.subject.meshCell Survival - Drug Effectsen_US
dc.subject.meshCeramides - Biosynthesis - Metabolismen_US
dc.subject.meshFatty Acids, Monounsaturated - Pharmacologyen_US
dc.subject.meshGpi-Linked Proteinsen_US
dc.subject.meshHela Cellsen_US
dc.subject.meshHumansen_US
dc.subject.meshLysosomes - Metabolismen_US
dc.subject.meshMembrane Proteins - Metabolismen_US
dc.subject.meshMicroscopy, Fluorescenceen_US
dc.subject.meshProtein Transport - Drug Effects - Physiologyen_US
dc.subject.meshProtozoan Proteins - Metabolismen_US
dc.subject.meshSphingolipids - Biosynthesisen_US
dc.subject.meshTrypanosoma Brucei Brucei - Metabolismen_US
dc.subject.meshVariant Surface Glycoproteins, Trypanosoma - Genetics - Metabolismen_US
dc.titleDe novo sphingolipid synthesis is essential for viability, but not for transport of glycosylphosphatidylinositol-anchored proteins, in African trypanosomesen_US
dc.typeArticleen_US
dc.identifier.emailSanyal, S: sumana@wi.mit.eduen_US
dc.identifier.authoritySanyal, S=rp01794en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1128/EC.00283-06en_US
dc.identifier.pmid17220466-
dc.identifier.scopuseid_2-s2.0-33947631189en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33947631189&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume6en_US
dc.identifier.issue3en_US
dc.identifier.spage454en_US
dc.identifier.epage464en_US
dc.identifier.isiWOS:000245475600010-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridSutterwala, SS=6507537874en_US
dc.identifier.scopusauthoridCreswell, CH=55809933800en_US
dc.identifier.scopusauthoridSanyal, S=16069600000en_US
dc.identifier.scopusauthoridMenon, AK=7202324192en_US
dc.identifier.scopusauthoridBangs, JD=7004912151en_US

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