Abstract
The vacuole of the yeast Saccharomyces cerevisiae plays an important role in nutrient storage. Arginine, in particular, accumulates in the vacuole of nitrogen-replete cells and is mobilized to the cytosol under nitrogen starvation. The arginine import and export systems involved remain poorly characterized, however. Furthermore, how their activity is coordinated by nitrogen remains unknown. Here we characterize Vsb1 as a novel vacuolar membrane protein of the APC (amino acid-polyamine-organocation) transporter superfamily which, in nitrogen-replete cells, is essential to active uptake and storage of arginine into the vacuole. A shift to nitrogen starvation causes apparent inhibition of Vsb1-dependent activity and mobilization of stored vacuolar arginine to the cytosol. We further show that this arginine export involves Ypq2, a vacuolar protein homologous to the human lysosomal cationic amino acid exporter PQLC2 and whose activity is detected only in nitrogen-starved cells. Our study unravels the main arginine import and export systems of the yeast vacuole and suggests that they are inversely regulated by nitrogen.
Highlights
The vacuole of the yeast Saccharomyces cerevisiae is the counterpart of the lysosome and has proved to be a valuable model for studying this organelle [1]
The lysosome-like vacuole of the yeast Saccharomyces cerevisiae is an important storage compartment for diverse nutrients, including the cationic amino acid arginine, which accumulates at high concentrations in this organelle in nitrogen-replete cells
When these cells are transferred to a nitrogen-free medium, vacuolar arginine is mobilized to the cytosol, where it is used as an alternative nitrogen source to sustain growth
Summary
The vacuole of the yeast Saccharomyces cerevisiae is the counterpart of the lysosome and has proved to be a valuable model for studying this organelle [1]. Dysfunction of a single lysosomal hydrolase or transporter can cause detrimental accumulation of non-recycled metabolites, the typical feature of lysosomal storage diseases (LSDs) [3]. One such disease, cystinosis, is caused by mutations in the CTNS gene encoding cystinosin, a lysosomal cystine exporter [4]. Patients suffering from cystinosis are treated with the aminothiol cysteamine This molecule enters the lysosomes and reacts there with accumulated cystine, converting it to cysteine and a cysteine-cysteamine mixed disulfide. The latter compound, structurally similar to lysine, is efficiently exported from the lysosomes via the PQLC2 cationic amino-acid exporter [5]
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