The role of
phosphoribosyl pyrophosphate synthetase (Prs) in cell wall integrity signalling
transduction in Saccharomyces cerevisiae.
Ke Wang (1),
Lilian M. Schweizer (1), Jürgen J Heinisch (2), Michael Schweizer (1)
(1) School of Life Sciences, Heriot-Watt University, Riccarton, Edinburgh, EH14
4AS, United Kingdom (Ke.Wang@hw.ac.uk); (2) Fachbereich Biologie/Chemie,
Universität Osnabrück, D-49076 Osnabrück, Germany
Phosphoribosyl-pyrophosphate synthetase (Prs) encoded by genes PRS1-PRS5 is a key enzyme in nucleotide metabolism and biosynthesis of histidine and tryptophan. To clarify the role of Prs in cell integrity pathway of S. cerevisiae, we investigated the sensitivity of prs Δ strains to various cell wall stress conditions known to activate Pkc1-regulated signalling transduction. Phenotypic analysis shows that deletion of PRS1 or PRS3 but not loss of PRS2, PRS4 or PRS5 results in hypersensitivity to high temperature (37°C), alpha-factor and caffeine and resistance to Calcofluor White indicating that Prs1p and Prs3p are involved in the maintenance of cell integrity. A role of Prs1p and Prs3p in the Pkc1-Mpk1 cascade is supported by findings: i) overexpression of PKC1 partially suppresses ts and alpha-factor sensitivity in PRS1 or PRS3 deletants, but not in a prs1 Δ prs3 Δ strain; ii) expression of the lacZ reporter gene under the control of Rlm1-dependent response element is reduced in strains lacking PRS1 and/or PRS3 under heat shock (39°C), alpha-factor treatment and optimal temperature (28°C). From investigations on strains carrying deletions of MID2 and PRS, it can be concluded that Prs1p and Prs3p function in parallel or upstream of the cell wall sensor Mid2p. Furthermore, at least one of the three minimal functional units Prs1p/Prs3p, Prs2p/Prs5p and Prs4p/Prs5p is found to be necessary in maintaining cell integrity after exposure to different stimuli.