Identification of Ftr1 and Zrt1 as iron and zinc micronutrient transceptors for activation of the PKA pathway in Saccharomyces cerevisiae

Joep Schothorst,Johan Thevelein,Griet Van Zeebroeck

doi:10.15698/mic2017.03.561

Joep Schothorst, Johan Thevelein + Show 1 more

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https://doi.org/10.15698/mic2017.03.561

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Abstract

Multiple types of nutrient transceptors, membrane proteins that combine a transporter and receptor function, have now been established in a variety of organisms. However, so far all established transceptors utilize one of the macronutrients, glucose, amino acids, ammonium, nitrate, phosphate or sulfate, as substrate. This is also true for the Saccharomyces cerevisiae transceptors mediating activation of the PKA pathway upon re-addition of a macronutrient to glucose-repressed cells starved for that nutrient, re-establishing a fermentable growth medium. We now show that the yeast high-affinity iron transporter Ftr1 and high-affinity zinc transporter Zrt1 function as transceptors for the micronutrients iron and zinc. We show that replenishment of iron to iron-starved cells or zinc to zinc-starved cells triggers within 1-2 minutes a rapid surge in trehalase activity, a well-established PKA target. The activation with iron is dependent on Ftr1 and with zinc on Zrt1, and we show that it is independent of intracellular iron and zinc levels. Similar to the transceptors for macronutrients, Ftr1 and Zrt1 are strongly induced upon iron and zinc starvation, respectively, and they are rapidly downregulated by substrate-induced endocytosis. Our results suggest that transceptor-mediated signaling to the PKA pathway may occur in all cases where glucose-repressed yeast cells have been starved first for an essential nutrient, causing arrest of growth and low activity of the PKA pathway, and subsequently replenished with the lacking nutrient to re-establish a fermentable growth medium. The broadness of the phenomenon also makes it likely that nutrient transceptors use a common mechanism for signaling to the PKA pathway.

Highlights

As a unicellular eukaryotic micro-organism, the yeast Saccharomyces cerevisiae has to be able to rapidly adapt to severe fluctuations in the extracellular conditions
We show that the yeast high-affinity iron transporter Ftr1 and high-affinity zinc transporter Zrt1 function as transceptors for the micronutrients iron and zinc
We have shown that activation of the PKA pathway targets by the other nutrients besides glucose, is mediated by high-affinity transporters induced during the starvation period that function as transporter-receptors or 'transceptors': Gap1 for amino acids [17, 18], Pho84 for phosphate [19,20,21], Mep2 for ammonium [5] and Sul1,2 for sulfate [22]

Summary

Introduction

As a unicellular eukaryotic micro-organism, the yeast Saccharomyces cerevisiae has to be able to rapidly adapt to severe fluctuations in the extracellular conditions. One of the most common adaptation mechanisms with respect to nutrient availability is the induction of high-affinity transporters for specific essential nutrients lacking or limiting in the medium, so that trace amounts of the sparse nutrient can be taken up efficiently by the microorganism. Examples of this adaptation mechanism have been described in yeast for all essential nutrients, i.e. the macronutrients glucose, nitrogen, phosphate and sulfate, and micronutrients like metal ions and vitamins. The high-affinity transporters generally undergo rapid downregulation upon re-exposure to their substrate through endocytic internalization, which is induced by

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