Document Detail

Identification of ISC1 (YER019w) as inositol phosphosphingolipid phospholipase C in Saccharomyces cerevisiae.
MedLine Citation:
PMID:  11006294     Owner:  NLM     Status:  MEDLINE    
Sphingolipids have emerged as novel bioactive mediators in eukaryotic cells including yeast. It has been proposed that sphingomyelin (SM) hydrolysis and the concomitant generation of ceramide are involved in various stress responses in mammalian cells. The yeast Saccharomyces cerevisiae has inositol phosphosphingolipids (IPS) instead of SM and glycolipids, and synthesis of IPS is indispensable to its growth. Although the genes responsible for the synthesis of IPS have been identified, the gene(s) for the degradation of IPS has not been reported. Here we show that ISC1 (YER019w), which has homology to bacterial neutral sphingomyelinase (SMase), encodes IPS phospholipase C (IPS-PLC). First, we observed that overexpression of ISC1 greatly increased neutral SMase activity, and this activity was dependent on the presence of phosphatidylserine. Cells deleted in ISC1 demonstrated negligible neutral SMase activity. Because yeast cells have IPS instead of SM, we investigated whether IPS are the physiologic substrates of this enzyme. Lysates of ISC1-overexpressing cells demonstrated very high PLC activities on IPS. Deletion of ISC1 eliminated endogenous IPS-PLC activities. Labeling yeast cells with [(3)H]dihydrosphingosine showed that IPS were increased in the deletion mutant cells. This study identifies the first enzyme involved in catabolism of complex sphingolipids in S. cerevisiae.
H Sawai; Y Okamoto; C Luberto; C Mao; A Bielawska; N Domae; Y A Hannun
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  275     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2001-01-08     Completed Date:  2001-02-08     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  39793-8     Citation Subset:  IM    
Department of Biochemistry and Molecular Biology and the Ralph H. Johnson Veterans Administration Hospital and the Department of Medicine, Medical University of South Carolina, Charleston 29425, USA.
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MeSH Terms
Blotting, Western
Detergents / pharmacology
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Gene Deletion
Hydrogen-Ion Concentration
Octoxynol / pharmacology
Phosphatidylserines / metabolism
Phospholipases / chemistry*,  genetics
Plasmids / metabolism
Saccharomyces cerevisiae / enzymology*
Saccharomyces cerevisiae Proteins
Sphingolipids / chemistry*,  metabolism
Sphingomyelin Phosphodiesterase / metabolism
Type C Phospholipases / chemistry*,  metabolism
Grant Support
Reg. No./Substance:
0/Cations; 0/Detergents; 0/Phosphatidylserines; 0/Saccharomyces cerevisiae Proteins; 0/Sphingolipids; 9002-93-1/Octoxynol; EC 3.1.-/Phospholipases; EC 3.1.4.-/ISC1 protein, S cerevisiae; EC 3.1.4.-/Type C Phospholipases; EC Phosphodiesterase

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