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Regulation of Osmotin Receptor Homologues in Yeast by Alterations in Lipid Metabolism
Author(s) -
Villa Nancy Y.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a89-d
Subject(s) - ergosterol , biochemistry , sphingolipid , biology , sterol , lipid metabolism , nystatin , saccharomyces cerevisiae , yeast , cholesterol , antibiotics
Saccharomyces cerevisiae possess four homologous genes encoding Progestin Adiponectin Receptors. Due to their proposed involvement in zinc homeostasis, these genes were named as IZH1‐4 ( I mplicated in Z inc H omeostasis). One of these genes, IZH2 , encodes the recently identified osmotin receptor. Using promoter‐reporter fusion constructs and western blots, we demonstrated that IZH2 and IZH4 are up‐regulated by both zinc, and hypoxia. Furthermore, we have confirmed that several of the IZH genes are regulated by exogenous fatty acids, suggesting a dual role in lipid metabolism. IZH2, for example was highly induced in the presence of myristate. Likewise, IZH1 and IZH3 were induced by palmitate, stearate, and oleate. It was previously reported that strains lacking IZH2 are resistance to nystatin, an antifungal that specifically binds to ergosterol in yeast. By using UV‐spectroscopy, we quantified the ergosterol content in wild type, and the mutants, izh2 Δ and izh3 Δ. In absence of nystatin, the ergosterol content was identical for the three strains, however in the presence of nystatin, izh3 Δ strain showed lower ergosterol content. Furthermore, the sterol 24‐(28)‐dehydroergosterol was also detected. These results, suggest a connection between the IZH genes and lipid metabolism, particularly sterol content. Finally, by using high performance liquid chromatography, we discovered that izh3 Δ presents an altered sphingolipid content. Sphingolipids and sterols form complex in the membranes called lipid rafts. Using high performance liquid chromatography, we have also found that the overexpression of the IZH genes causes increased levels of certain sphingolipids, implicating these genes in the sphingolipid metabolism. This research has been supported by the University of Florida, Chemistry Department.