G-protein coupled receptors regulate morphological development in the plant pathogen Ustilago maydis

G-protein-coupled receptors (GPCRs) are the largest class of eukaryotic receptor proteins that regulate physiology and are important drug targets in humans. Although GPCRs are present in fungi and might be similarly druggable, they are far less understood than their human counterparts. This is of particular interest, as pathogenic fungi are gaining increasing attention, as human-, animal- and plant diseases caused by fungi are on the rise. Therefore, a mechanistic understanding of fungal GPCRs is crucially lacking.
In my project, we investigate the contribution of GPCRs to the pathogenicity of the basidiomycete fungus Ustilago maydis. In a first step, more than 30 previously undescribed proteins that share structural similarity with 7-transmembrane GPCRs were discovered on the genome of U. maydis. These potential GPCRs are highly diverse on the sequence level and many are not conserved in well-studied ascomycete fungi and might be an adaptation to its specific plant-pathogenic lifestyle. A closer inspection of the expression profiles of the GPCR candidates showed that many are differentially expressed during infection of the host Zea mays. We therefore hypothesize that these receptors enable the fungus to detect host-specific signals but likely also metabolites. Some of these stimuli might also be important for regulating the dimorphic switch from yeast-like sporidia to infectious hyphae in U. maydis.
To first gain more knowledge on their potential functions, we not only performed a structure-guided categorization of the receptors but also used structure prediction tools to predict interactions between the receptors and the four Gα-subunits of U. maydis. We are currently implementing a yeast reporter system that allows us to identify different ligands recognized by the receptors and understand the importance of these signals for pathogenic development of U. maydis.
Since GPCR signal transduction is linked to the secondary messenger cAMP, we also determined cAMP levels revealing that different GPCR deletion backgrounds are decreased in cAMP. These results further suggest that some of the studied receptors are indeed GPCRs and linked to the cAMP signaling pathway of U. maydis.
Our research will contribute to a better understanding of fungal GPCRs in terms of signal transduction, its link to cAMP levels and overall pathogenicity in U. maydis. These findings will provide a basis for detailed GPCR-ligand interactions and enhance our understanding of signal perception in pathogenic basidiomycete fungi.