We identified invadolysin, a novel essential metalloprotease, for functions in chromosome
structure, cell proliferation and migration. Invadolysin also plays an important metabolic
role in insulin signalling and is the only protease known to localise to lipid droplets,
the main lipid storage organelle in the cell. In silico examination of the protein
sequence of invadolysin predicts not only protease and lipase catalytic motifs, but
also post-translational modifications and the secretion of invadolysin. Here we show
that the protease motif of invadolysin is important for its role in lipid accumulation,
but not in glycogen accumulation. The lipase motif does not appear to be functionally
important for the accumulation of lipids or glycogen. Post-translational modifications
likely contribute to modulating the level, localisation or activity of invadolysin.
We identified a secreted form of invadolysin in the soluble fraction of invertebrate
hemolymph (where we observe sexually dimorphic forms) and also vertebrate plasma,
including in the extracellular vesicle fraction. Biochemical analysis for various
post-translational modifications demonstrated that secreted invadolysin is both N-
and O-glycosylated, but not apparently GPI-linked. The discovery of invadolysin in
the extracellular milieu suggests a role for invadolysin in normal organismal physiology.