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Final Activity Report Summary - PI SIGNALLING (Phosphate sensing for activation of the protein kinase A pathway in yeast)

Specific nutrient transporters in eukaryotic cells have recently been suggested to function as nutrient receptors for activation of signalling pathways. In the yeast Saccharomyces cerevisiae, the Pho84 phosphate transporter appears to mediate phosphate-induced activation of the PKA pathway in phosphate-starved cells. We showed that addition of phosphate-containing compounds such as glycerol-3-phosphate (Gly3P) or glycerophosphoinositol (GlyPIno) to phosphate-starved cells triggers rapid activation of trehalase, a well-known protein kinase A (PKA) target. The activation is reduced in mutants with reduced PKA activity and is independent of secreted phosphatase activity. Pho84 is required as for Gly3P- and also for GlypIno-induced trehalase activation but is unable to transport these compounds.

The known transporter of GlyPIno is encoded by GIT1 gene. First we discovered that Gly3P is transported inside the cell by Pho91, which is more known as a weak low-affinity phosphate transporter, and Git1 permease. We also showed that the lethality of a yeast phosphate carrier null strain can be rescued by addition of Gly3P as a Pi source and that the Gly3P is taken up in this case by the Git1 carrier. However, deletion of Git1 does not prevent Gly3P-induced trehalase activation nor is Git1 able to support the activation of trehalase.

The same is true for the phosphate carriers Pho87, Pho90 and Pho91.Competitive inhibition of phosphate transport by Gly3P or GlyPIno confirms interaction of Gly3P and GlyPIno with the phosphate-binding site of Pho84. These results support the role of Pho84 as a phosphate sensor. We have found the first non-transported agonists of the signalling function of a transporter-receptor identified in eukaryotic cells.

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