Invadolysin (green) localizes to structures resembling invadopodia.

In a search for proteins involved in chromosome condensation, McHugh et al. (page 673) have identified a novel metalloprotease, IX-14/invadolysin, that is required for both mitosis and cell motility in Drosophila, and probably also in human cells.

The mutation, identified in a chemical mutagenesis screen, blocks cell proliferation as evidenced by underdeveloped brains and imaginal discs in larvae. It disrupts compaction of both interphase and mitotic chromosomes, such that mitotic chromosomes are hypercondensed in length but with a loose peripheral halo of chromatin. The mutation also results in aberrant spindle assembly and increased levels of some nuclear envelope proteins. Possible substrates for the metalloprotease that might explain these phenotypes are unknown, but enzyme assays did suggest that invadolysin can cleave the nuclear envelope protein lamin Dm0. By contrast, previous studies of lamin changes during mitosis had focused on phosphorylation.

In human cells, the majority of the protein was in ring-shaped formations that resemble invadopodia. These structures help degrade extracellular matrix and thus aid metastasis. Consistent with a possible role in cell migration, invadolysin localizes to the leading edge of motile macrophages. Returning to Drosophila, the team found that germ cells failed to migrate normally in mutant embryos, indicating that the protein is also involved in cell migration in flies.

Given that invadolysin seems to have its fingers in diverse processes, McHugh et al. hypothesize there are multiple forms of the protein that may be differentially regulated and localized. These forms may link the related processes of cell growth and migration.