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Journal article
Yeast cells lacking the ARV1 gene harbor defects in sphingolipid metabolism. Complementation by human ARV1
The Journal of biological chemistry, v 277(39), pp 36152-36160
27 Sep 2002
PMID: 12145310
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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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Details
- Title
- Yeast cells lacking the ARV1 gene harbor defects in sphingolipid metabolism. Complementation by human ARV1
- Creators
- Evelyn Swain - Hahnemann University HospitalJoseph Stukey - Hope CollegeVirginia McDonough - Hope CollegeMelody Germann - Hahnemann University HospitalYing Liu - Columbia UniversityStephen L Sturley - Columbia UniversityJoseph T Nickels, JrJoseph T Nickels - Biochemistry and Molecular Biology
- Publication Details
- The Journal of biological chemistry, v 277(39), pp 36152-36160
- Publisher
- ASBMB Publications / Elsevier
- Grant note
- HL67401-01A1 / NHLBI NIH HHS DK54320 / NIDDK NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000178275100050
- Scopus ID
- 2-s2.0-0037183971
- Other Identifier
- 991019168706504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology