Inhibition of amino acid transport by sphingoid long chain bases in Saccharomyces cerevisiae

Marek S. Skrzypek, M. Marek Nagiec, Robert L. Lester, Robert C. Dickson

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Sphingoid long chain bases have many effects on cells including inhibition or stimulation of growth. The physiological significance of these effects is unknown in most cases. To begin to understand how these compounds inhibit growth, we have studied Saccharomyces cerevisiae cells. Growth of tryptophan (Trp-) auxotrophs was more strongly inhibited by phytosphingosine (PHS) than was growth of Trp+ strains, suggesting that PItS diminishes tryptophan uptake and starves cells for this amino acid. This hypothesis is supported by data showing that growth inhibition is relieved by increasing concentrations of tryptophan in the culture medium and by multiple copies of the TAT2 gene, encoding a high affinity tryptophan transporter. Measurement of tryptophan uptake shows that it is inhibited by PHS. Finally, PHS treatment induces the general control response, indicating starvation for amino acids. Multiple copies of TAT2 do not protect cells against two other cationic lipids, stearylamine, and sphingosine, indicating that the effect of PHS on tryptophan utilization is specific. Other data demonstrate that PHS reduces uptake of leucine, histidine, and proline by specific transporters. Our data suggest that PHS targets proteins in the amino acid transporter family but not other distantly related membrane transporters, including those necessary for uptake of adenine and uracil.

Original languageEnglish
Pages (from-to)2829-2834
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number5
DOIs
StatePublished - Jan 30 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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