Abstract for presentation at 11th International Congress of Human Genetics

We are investigating the role of genes involved in the response to nutrient depletion using as a model extracellular protease production in the filamentous fungus, Aspergillus nidulans. In A. nidulans, extracellular proteases are produced in response to carbon-, nitrogen- or sulfur-nutrient limitation. We have shown that two atypical hexokinases (XprF and HxkC), which we believe are non-catalytic, are involved in the regulation of extracellular protease production in A. nidulans. In addition, we have identified a third protein (XprG) that is involved in the response to starvation. The xprG gene product belongs to a newly defined class of DNA-binding proteins which includes a transcriptional activator required for progression through meiosis in yeast and a human protein shown to be highly expressed in metastatic tumour cells.
Strains carrying an xprG- null mutation do not produce extracellular proteases in response to nutrient limitation. We have isolated revertants of an xprG- mutant which have regained the ability to produce extracellular protease. The revertants carry mutations in genes which we have named suppressors of xprG (sogA, sogB and sogC). Two of the revertants carry chromosome rearrangements. A combination of genetic mapping and Southern blot analysis was used to show that the translocation breakpoint in the sogA1 mutant was located in a gene encoding a sorting nexin (VPS5). Transformation with a wild type copy of the gene confirmed that we had identified the sogA gene. Preliminary mapping data suggests that the sogB and sogC genes also encode components of the multivesicular body pathway which sorts cell surface receptors and membrane proteins.