The conserved metalloprotease invadolysin is present in invertebrate haemolymph and vertebrate blood

Abstract

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.

Metalloenzyme Inhibitors against Zoonotic Infections: Focus on Leishmania and Schistosoma

“…113 This 63 kDa metalloprotease belongs to the metzincin class and is the representative member of the family M8 of metalloproteases, in addition to the newly identified invadolysin. 114 gp63 features a conserved sequence motif of HExxHxxGxxH, along with an N-terminal pro-peptide that renders the pro-enzyme inactive during translation. This pro-peptide is subsequently removed during maturation and activation, allowing for enzymatic activity.…”

“…Among the protozoan metalloproteases we can find leishmanolysin, or gp63, discovered in the early 1980s and extensively studies since then owing to its abundance and role in virulence . This 63 kDa metalloprotease belongs to the metzincin class and is the representative member of the family M8 of metalloproteases, in addition to the newly identified invadolysin . gp63 features a conserved sequence motif of HExxHxxGxxH, along with an N-terminal pro-peptide that renders the pro-enzyme inactive during translation.…”