Role of regulated proteolysis in the response to cation stress and alkaline pH tolerance of Aspergillus nidulans

Three regulatory systems coexist in Aspergillus nidulans and other filamentous fungi to provide with adequate response to ambient alkaline pH and excess of cations. The calcineurin-dependent transcription factor CrzA is required for growth at alkaline pH and in conditions of high extracellular calcium concentrations. PacC is the well known regulator of ambient pH signaling and SltA is required for tolerance to high alkali-cation concentrations and to alkalinity. CrzA and PacC homologues are present in almost all known fungal genomes, however SltA homologues can only be found in species of Pezizomycotina subphylum. All these transcription factors are subjected to posttranslational modifications for modulating their activities. Particularly PacC and SltA are subjected an irreversible posttranslational modification, egulated proteolysis. Here we present our analysis of the Slt regulatory system. SltA is synthesized in a 78 kDa form which is proteolysed to a functional 32 kDa form. SltB is the second element identified in this pathway. SltB is probably a bi-functional protein, with a pseudo-kinase domain and a chymotrypsin-like domain. Our studies identified SltB as the protease involved in SltA78kDa to SltA32kDa proteolysis. Notably, SltB is also subjected to a proteolytic step to become active. Interestingly, suppressors of poor growth phenotype derived of deletion of vps genes provided us with a large battery of mutations affecting either sltA or sltB. Characterization of these mutations is allowing us to decipher the mechanism of SltA signaling. In this presentation we will show our current knowledge of the Slt pathway.