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In many microorganisms the control of cellular adhesion plays a crucial role in establishing contact to various environmental habitats. This also includes the budding yeast Saccharomyces cerevisiae that is capable of adapting its adhesive properties to changes in the environment. S. cerevisiae possesses a set of cell surface glycoproteins – the flocculins – which belong to the family of fungal GPI-linked adhesins. A key flocculin for adhesion to agar and plastic surfaces is Flo11. FLO11 gene expression underlies the complex control of numerous signaling pathways that converge on the exceptionally large FLO11 promoter and respond to diverse environmental stimuli.
In this work, the regulation of the Flo11-dependent adhesion by external pH was investigated in detail. One focus was on the Rim101 signaling pathway, which is highly conserved in fungi and confers pH-dependent regulation of diverse cellular processes. The results obtained demonstrate that the Rim101 signaling pathway of S. cerevisiae plays a central role in controlling Flo11-dependent adhesion under acidic and neutral conditions. It was found that the transcriptional repressor Rim101 indirectly regulates FLO11 expression by controlling expression of the genes for the transcriptional repressors Nrg1, Nrg2 and Smp1, hereby. Several DNA elements within the FLO11 promoter could be identified and characterized that confer in vitro binding and in vivo regulation by Nrg1 and Nrg2. Genome-wide transcriptional analysis revealed that FLO11 belongs to a large group of genes that are strongly regulated during the shift from neutral to alkaline pH. It was found that FLO11 expression and Flo11-dependent adhesion are strongly down-regulated under alkaline conditions. The reduction of FLO11 expression occurs independent of the Rim101 signaling pathway by a yet unknown regulatory system. Finally cell biological measurements suggest that an alteration of cell surface peptides – possibly induced by inactivation of the Flo11-protein may be an additional cause for the distinctive loss of adhesion under alkaline conditions.