Abstract
Saccharomyces cerevisiae transcriptionally regulates the expression of the plasma membrane high affinity iron transport system in response to iron need. This transport system is comprised of the products of the FET3 and FTR1 genes. We show that Fet3p and Ftr1p are post-translationally regulated by iron. Incubation of cells in high iron leads to the internalization and degradation of both Fet3p and Ftr1p. Yeast strains defective in endocytosis (Deltaend4) show a reduced iron-induced loss of Fet3p-Ftr1p. In cells with a deletion in the vacuolar protease PEP4, high iron medium leads to the accumulation of Fet3p and Ftr1p in the vacuole. Iron-induced degradation of Fet3p-Ftr1p is significantly reduced in strains containing a deletion of a gene, VTA1, which is involved in multivesicular body (MVB) sorting in yeast. Sorting through the MVB can involve ubiquitination. We demonstrate that Ftr1p is ubiquitinated, whereas Fet3p is not ubiquitinated. Iron-induced internalization and degradation of Fet3p-Ftr1p occurs in a mutant strain of the E3 ubiquitin ligase RSP5 (rsp5-1), suggesting that Rsp5p is not required. Internalization of Fet3p-Ftr1p is specific for iron and requires both an active Fet3p and Ftr1p, indicating that it is the transport of iron through the iron permease Ftr1p that is responsible for the internalization and degradation of the Fet3p-Ftr1p complex.
Highlights
Transition metals are essential for life, yet transition metals in high concentrations can be toxic
To determine if the Fet3p-Ftr1p transport system is posttranscriptionally regulated by iron, we exposed wild type cells expressing the transport system to high iron medium and examined Fet3p levels by Western analysis
When cells were exposed to high iron medium there was a concentration-dependent decrease in Fet3p
Summary
Transition metals are essential for life, yet transition metals in high concentrations can be toxic. High affinity iron transport in the budding yeast Saccharomyces cerevisiae requires the expression of two cell surface proteins, the multicopper oxidase Fet3p and the transmembrane permease Ftr1p [1, 2]. Transcription of these genes, as well as genes that encode proteins required for the processing of Fet3p, is regulated by the iron sensing transcription factor Aft1p [3]. There is a 50% reduction in transport activity when such cells are incubated in high iron as opposed to low iron medium [8] Based on these observations, we re-examined whether the Fet3p-Ftr1p transport system is post-translationally regulated. We demonstrate that high levels of iron induce the internalization and degradation of the Fet3p-Ftr1p transport system
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