JBC Anatrace, Inc.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M204115200 on May 10, 2002

J. Biol. Chem., Vol. 277, Issue 29, 26177-26184, July 19, 2002
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
277/29/26177    most recent
M204115200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Swain, E.
Right arrow Articles by Nickels, J. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Swain, E.
Right arrow Articles by Nickels, J. T., Jr.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Sterol-dependent Regulation of Sphingolipid Metabolism in Saccharomyces cerevisiae*

Evelyn SwainDagger , Karen BaudryDagger , Joseph Stukey§, Virginia McDonough§, Melody GermannDagger , and Joseph T. Nickels Jr.Dagger

From the Dagger  Department of Biochemistry, MCP Hahnemann University, Philadelphia, Pennsylvania 19102 and the § Department of Biology, Hope College, Holland, Michigan 49423

We had previously isolated the temperature-sensitive erg26-1 mutant and characterized the sterol defects in erg26-1 cells (Baudry, K., Swain, E., Rahier, A., Germann, M., Batta, A., Rondet, S., Mandala, S., Henry, K., Tint, G. S., Edlind, T., Kurtz, M., and Nickels, J. T., Jr. (2001) J. Biol. Chem. 276, 12702-12711). We have now determined the defects in sphingolipid metabolism in erg26-1 cells, examined their effects on cell growth, and initiated studies designed to elucidate how might changes in sterol levels coordinately regulate sphingolipid metabolism in Saccharomyces cerevisiae. Using [3H]inositol radiolabeling studies, we found that the biosynthetic rate and steady-state levels of specific hydroxylated forms of inositolphosphorylceramides were decreased in erg26-1 cells when compared with wild type cells. [3H]Dihydrosphingosine radiolabeling studies demonstrated that erg26-1 cells had decreased levels of the phytosphingosine-derived ceramides that are the direct precursors of the specific hydroxylated inositol phosphorylceramides found to be lower in these cells. Gene dosage experiments using the sphingolipid long chain sphingoid base (LCB) hydroxylase gene, SUR2, suggest that erg26-1 cells may accumulate LCB, thus placing one point of sterol regulation of sphingolipid synthesis possibly at the level of ceramide metabolism. The results from additional genetic studies using the sphingolipid hydroxylase and copper transporter genes, SCS7 and CCC2, respectively, suggest a second possible point of sterol regulation at the level of complex sphingolipid hydroxylation. In addition, [3H]inositol radiolabeling of sterol biosynthesis inhibitor-treated wild type cells and late sterol pathway mutants showed that additional blocks in sterol biosynthesis have profound effects on sphingolipid metabolism, particularly sphingolipid hydroxylation state. Finally, our genetic studies in erg26-1 cells using the LCB phosphate phosphatase gene, LBP1, suggest that increasing the levels of the LCB sphingoid base phosphate can remediate the temperature-sensitive phenotype of erg26-1 cells.

* This work was supported by National Institutes of Health Grant HL67401-01A1 (to J. T. N.), a Basil O'Connor Starter Scholarship Award (to J. T. N.), and an Atorvastatin Research Award (to V. M.) sponsored by Pfizer Inc.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: (215)-762-1941; Fax: (215) 762-4452; E-mail: Joseph.Nickels@drexel.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
V. Meyer, R. A. Damveld, M. Arentshorst, U. Stahl, C. A. M. J. J. van den Hondel, and A. F. J. Ram
Survival in the Presence of Antifungals: GENOME-WIDE EXPRESSION PROFILING OF ASPERGILLUS NIGER IN RESPONSE TO SUBLETHAL CONCENTRATIONS OF CASPOFUNGIN AND FENPROPIMORPH
J. Biol. Chem., November 9, 2007; 282(45): 32935 - 32948.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
D. Kunze, D. MacCallum, F. C. Odds, and B. Hube
Multiple functions of DOA1 in Candida albicans
Microbiology, April 1, 2007; 153(4): 1026 - 1041.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
M. Valachovic, B. M. Bareither, M. S. A. Bhuiyan, J. Eckstein, R. Barbuch, D. Balderes, L. Wilcox, S. L. Sturley, R. C. Dickson, and M. Bard
Cumulative Mutations Affecting Sterol Biosynthesis in the Yeast Saccharomyces cerevisiae Result in Synthetic Lethality That Is Suppressed by Alterations in Sphingolipid Profiles
Genetics, August 1, 2006; 173(4): 1893 - 1908.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
M. Pittet, D. Uldry, M. Aebi, and A. Conzelmann
The N-glycosylation defect of cwh8{Delta} yeast cells causes a distinct defect in sphingolipid biosynthesis
Glycobiology, February 1, 2006; 16(2): 155 - 164.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
V. Zaremberg, C. Gajate, L. M. Cacharro, F. Mollinedo, and C. R. McMaster
Cytotoxicity of an Anti-cancer Lysophospholipid through Selective Modification of Lipid Raft Composition
J. Biol. Chem., November 11, 2005; 280(45): 38047 - 38058.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Sano, A. Kihara, F. Kurotsu, S. Iwaki, and Y. Igarashi
Regulation of the Sphingoid Long-chain Base Kinase Lcb4p by Ergosterol and Heme: STUDIES IN PHYTOSPHINGOSINE-RESISTANT MUTANTS
J. Biol. Chem., November 4, 2005; 280(44): 36674 - 36682.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
T. Prasad, P. Saini, N. A. Gaur, R. A. Vishwakarma, L. A. Khan, Q. M. R. Haq, and R. Prasad
Functional Analysis of CaIPT1, a Sphingolipid Biosynthetic Gene Involved in Multidrug Resistance and Morphogenesis of Candida albicans
Antimicrob. Agents Chemother., August 1, 2005; 49(8): 3442 - 3452.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
K. Mukhopadhyay, T. Prasad, P. Saini, T. J. Pucadyil, A. Chattopadhyay, and R. Prasad
Membrane Sphingolipid-Ergosterol Interactions Are Important Determinants of Multidrug Resistance in Candida albicans
Antimicrob. Agents Chemother., May 1, 2004; 48(5): 1778 - 1787.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. K. Agarwal, P. D. Rogers, S. R. Baerson, M. R. Jacob, K. S. Barker, J. D. Cleary, L. A. Walker, D. G. Nagle, and A. M. Clark
Genome-wide Expression Profiling of the Response to Polyene, Pyrimidine, Azole, and Echinocandin Antifungal Agents in Saccharomyces cerevisiae
J. Biol. Chem., September 12, 2003; 278(37): 34998 - 35015.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
K. Mukhopadhyay, A. Kohli, and R. Prasad
Drug Susceptibilities of Yeast Cells Are Affected by Membrane Lipid Composition
Antimicrob. Agents Chemother., December 1, 2002; 46(12): 3695 - 3705.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
M. Eisenkolb, C. Zenzmaier, E. Leitner, and R. Schneiter
A Specific Structural Requirement for Ergosterol in Long-chain Fatty Acid Synthesis Mutants Important for Maintaining Raft Domains in Yeast
Mol. Biol. Cell, December 1, 2002; 13(12): 4414 - 4428.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Swain, J. Stukey, V. McDonough, M. Germann, Y. Liu, S. L. Sturley, and J. T. Nickels Jr.
Yeast Cells Lacking the ARV1 Gene Harbor Defects in Sphingolipid Metabolism. COMPLEMENTATION BY HUMAN ARV1
J. Biol. Chem., September 20, 2002; 277(39): 36152 - 36160.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.