We have utilised Drosophila as a model system to identify novel and conserved genes essential for progression through the cell cycle and normal cellular physiology. Invadolysin is a zinc-metalloprotease that we have shown to link cell division and cell migration in D. melanogaster (McHugh et al., 2004). Invadolysin localises to lipid droplets in mammalian cell lines, and Drosophila invadolysin mutants have a decreased triglyceride:protein ratio (Cobbe et al., 2009). Invadolysin additionally interacts with mitochondrial ATP synthase subunits (Di Cara et al., 2013) and plays a role in angiogenesis (Vass and Heck, 2013). As many proteases function in catalytic pathways, it is intriguing that the first genetic interactor of invadolysin is a ubiquitin protease – targeting histone H2B, and thereby linking to the chromosome defects we observe (Gururaja Rao et al., 2015). Invadolysin is the first metalloprotease localised to lipid droplets, and physiological functions remain at this point speculative.
We have very recently discovered that a secreted form of invadolysin is present in vertebrate serum and Drosophila hemolymph. As the gene is essential for life, we hypothesise that the secreted form of invadolysin may be playing a role crucial to normal physiology. We aim to discover whether invadolysin is present in a particular serum compartment (such as exosomes or microvesicles) and whether proteolytic activity for invadolysin can be detected. Should activity be detected, we can begin to ask questions pertaining to the regulation of localization, levels and activity. Importantly, we will be able to address whether this novel form of invadolysin serves as a potential biomarker for any human disease states.