Elevation of endogenous sphingolipid long-chain base phosphates kills Saccharomyces cerevisiae cells

Xiping Zhang, Marek S. Skrzypek, Robert L. Lester, Robert C. Dickson

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Sphingolipid long-chain base phosphates (LCBPs) regulate cell proliferation, movement and differentiation in higher eukaryotes. To study the function of LCBPs in Saccharomyces cerevisiae, we inactivated LCBP breakdown pathways. Elimination of both the Dp11 lyase and the Lcb3 phosphatase pathways by gene deletion was lethal, indicating that these enzymes regulate LCBP levels to prevent accumulation. Lethality was prevented by eliminating the major LCB kinase, Lcb4p, which synthesizes LCBPs, but not by eliminating the minor LCB kinase, Lcb5p. These data imply that death results from an accumulation of LCBPs made by the Lcb4p kinase. By regulating Lcb4 kinase activity, we found that cell death correlates with LCBP accumulation and that C18 dihydrosphingosine-1-P (DHS-P) and C20 DHS-P are most likely the killing molecules. LCB levels were found to be most elevated in a strain lacking Lcb4 kinase. Dp11 lyase and Lcb3 phosphatase activity. Analysis of mutant strains suggests that the C18 and C20 species of LCBPs are preferentially degraded by the Lcb3 phosphate phosphatase, while the Dp11 lyase prefers C16 DHS-P as a substrate. These and other data indicate the existence of an unknown mechanism(s) for regulating LCB levels. Our results demonstrate that LCBPs may be used in some circumstances to regulate yeast cell growth.

Original languageEnglish
Pages (from-to)221-233
Number of pages13
JournalCurrent Genetics
Volume40
Issue number4
DOIs
StatePublished - 2001

Bibliographical note

Funding Information:
Acknowledgement This work was supported by National Institutes of Health Grant GM58507.

Keywords

  • Growth control
  • Sphingolipids
  • Sphingosine kinase
  • Sphingosine-1-phosphate

ASJC Scopus subject areas

  • Genetics

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