Endocrine Abstracts

The classic Drosophila model system has been utilized by the Heck laboratory for the characterization of novel and conserved genes essential for cell cycle and cellular physiology. The invadolysin mutation was first identified in D. melanogaster, which gave rise to abnormally-condensed chromosomes and had a lethal effect on the late larval stages. Invadolysin is a novel zinc-metalloprotease that we have shown to link cell division and cell migration in D. melanogaster. Invadolysin localizes to lipid droplets in mammalian cell lines, and Drosophila invadolysin mutants have a decreased triglyceride:protein ratio. Invadolysin also plays a role in insulin signalling and adipogenesis - in the fly and in vertebrate in vitro models. Recently, we discovered an extracellular form of invadolysin in Drosophila hemolymph and human plasma, and invadolysin is present in the extracellular vesicle-enriched fraction of human plasma. As invadolysin is essential for life, we are suggesting that the secreted form of invadolysin may play an important role in maintaining normal physiology. In this research, we are developing biochemical strategies to enrich invadolysin from human plasma, which improves the detection and analysis of the extracellular form of invadolysin. Preliminary results reveal that the extracellular form(s) of invadolysin differ between the enriched fractions of human serum and plasma. We are looking to understand these differences, and detect associated enzymatic activity of the secreted form(s) of invadolysin. Importantly, our long-term aim is to address whether the secreted form(s) of invadolysin play a role in normal physiology or serve as a potential biomarker for any human disease states.