Function of the essential leishmanolysin-related protease invadolysin in flies and man

Invadolysin is a novel essential metalloprotease that is conserved among metazoans. We have demonstrated a localisation of the protein to lipid droplets, the dynamic fat storage organelle of the cell. We also showed that Drosophila that lacked invadolysin accumulated significantly lower levels of fat, and exhibited impaired insulin signalling while the level of invadolysin increased in in vitro adipogenesis models. We have very recently discovered that invadolysin is present in vertebrate serum and invertebrate hemolymph.

We will investigate what role this essential enzyme may play in common pathological states in humans, such as obesity and diabetes. We will ask whether invadolysin can be localised to a specific fraction of human serum, and if proteolytic activity can be detected therein. We also plan to characterise the catalytic motif(s) of invadolysin to discern their role in its function. Detailed phenotypic analysis will be performed on recently generated transgenic Drosophila expressing forms of invadolysin in which the conserved metalloprotease and a potential lipase motif have been mutated.

The combination of approaches in vertebrate and invertebrate systems will shed light on the role of invadolysin and generate crucial pilot data for future research grant applications.