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Yeast cells lacking the ARV1 gene harbor defects in sphingolipid metabolism. Complementation by human ARV1
Journal article   Open access   Peer reviewed

Yeast cells lacking the ARV1 gene harbor defects in sphingolipid metabolism. Complementation by human ARV1

Evelyn Swain, Joseph Stukey, Virginia McDonough, Melody Germann, Ying Liu, Stephen L Sturley, Joseph T Nickels, Jr and Joseph T Nickels
The Journal of biological chemistry, v 277(39), pp 36152-36160
27 Sep 2002
DOI: https://doi.org/10.1074/jbc.M206624200
PMID: 12145310
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1074/jbc.m206624200View
Published, Version of Record (VoR)CC BY V4.0,  Open
url
https://doi.org/10.1074/jbc.M206624200View
Published, Version of Record (VoR) Open

Abstract

Ceramides - metabolism DNA, Complementary - metabolism Endoplasmic Reticulum - metabolism Gas Chromatography-Mass Spectrometry Genetic Complementation Test Golgi Apparatus - metabolism Green Fluorescent Proteins Humans Inositol - metabolism Lipid Metabolism Luminescent Proteins - metabolism Membrane Proteins - chemistry Membrane Proteins - genetics Membrane Proteins - metabolism Microscopy, Fluorescence Mutation Plasmids - metabolism Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae Proteins - chemistry Saccharomyces cerevisiae Proteins - genetics Saccharomyces cerevisiae Proteins - metabolism Sphingolipids - metabolism Sphingosine - analogs & derivatives Sphingosine - metabolism Temperature Time Factors
arv1Delta mutant cells have an altered sterol distribution within cell membranes (Tinkelenberg, A.H., Liu, Y., Alcantara, F., Khan, S., Guo, Z., Bard, M., and Sturley, S. L. (2000) J. Biol. Chem. 275, 40667-40670), and thus it has been suggested that Arv1p may be involved in the trafficking of sterol in the yeast Saccharomyces cerevisiae and also in humans. Here we present data showing that arv1Delta mutants also harbor defects in sphingolipid metabolism. [(3)H]inositol and [(3)H]dihydrosphingosine radiolabeling studies demonstrated that mutant cells had reduced rates of biosynthesis and lower steady-state levels of complex sphingolipids while accumulating certain hydroxylated ceramide species. Phospholipid radiolabeling studies showed that arv1Delta cells harbored defects in the rates of biosynthesis and steady-state levels of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. Neutral lipid radiolabeling studies indicated that the rate of biosynthesis and steady-state levels of sterol ester were increased in arv1Delta cells. Moreover, these same studies demonstrated that arv1Delta cells had decreased rates of biosynthesis and steady-state levels of total fatty acid and fatty acid alcohols. Gas chromatography/mass spectrometry analyses examining different fatty acid species showed that arv1Delta cells had decreased levels of C18:1 fatty acid. Additional gas chromatography/mass spectrometry analyses determining the levels of various molecular sterol species in arv1Delta cells showed that mutant cells accumulated early sterol intermediates. Using fluorescence microscopy we found that GFP-Arv1p localizes to the endoplasmic reticulum and Golgi. Interestingly, the heterologous expression of the human ARV1 cDNA suppressed the sphingolipid metabolic defects of arv1Delta cells. We hypothesize that in eukaryotic cells, Arv1p functions in the sphingolipid metabolic pathway perhaps as a transporter of ceramides between the endoplasmic reticulum and Golgi.

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Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
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