In a living animal without cancer, the extracellular matrix is an odd place to find a cathepsin B-like protein.
I am a PhD student in developmental and cell biology. My studies require a working laboratory knowledge of how to manipulate the genomes of fruit flies to study how cells interact during development by altering gene expression and creating mutant proteins. This includes a self-sustaining understanding of basic genomics and proteomics, molecular biology, cell culture, developmental processes at the cellular and organismal level, and a natural curiosity to spend enough devoted to figuring out a specific problem in developmental biology.
In my case, I am examining what at intuition says "disease condition," when it's heard. This condition is the presence of a cathepsin B-like protein in the extracellular matrix. For those of you not familiar with cathepsins (or protein families in general, for that matter), they are a type of protein that cuts other proteins into smaller pieces, or proteases for short. Cathepsins are normally found in lysosomes, which are acidic vesicles within cells containing an array of proteases involved in recycling other proteins in the cell. However, in many cancers, cathepsins can be secreted into the extracellular matrix where they can digest away basement membranes, thus promoting tumor invasion. So cathepsin B or a cathepsin B-like protein in the extracellular matrix is considered a bad thing.
However it was, to my surprise, that there was an extracellular matrix molecule (a protein) that contained a cathepsin B-like domain that is catalytically inactive. There is no reported evidence of any activity from the few studies conducted on a mouse version of this protein. Supporting evidence includes the presence of an amino acid mutation from a cysteine in the active site to a serine (cathepsins belong to a larger family called cysteine proteases). While there is also a giant family of serine proteases, they do not share sequence homology with cathepsin B. In experiments with mouse kidneys where this gene was blocked, the epithelial tubules failed to form with much of the epithelial tissue never even differentiating from the mesenchyme.
So it appears that the structural properties of an inert cathepsin B have become important in the development of multicellular organisms by serving some function outside of cells. In fruit flies, I see this gene expressed in cells undergoing unique morphogenetic processes during tissue migrations in development. Through nifty genetic tactics, I have engineered a strain of flies that lack the gene in this extracellular cathepsin b-like protein. We know it's essentially required in the mother during oogenesis to proceed normally both in terms of egg development and embyro development. The maternally provided protein to the embryo allows it to be sustained relatively late in larval life when they start to form cysts of their own tissues encapsulated by melanizing "blood cells" in something akin to an immune response. Removal of the maternally provided RNA through more nifty genetic tactics shows the protein is essential for normal embryonic development (with a small percentage of "escapers" <1%).
So the gene appears to be required for development of flies...and of kidneys in more complex vertebrates. At the cellular level, the protein is possibly serving a very similar purpose. My aim is to find a specific interaction of this protein with cells and use phenotypic rescue to test which parts of the protein are most vital for proper function.
I post this as an example of the numerous genes which are conserved not only from flies to humans. But keep in mind there are genes conserved among bacteria and humans including those responsible for synthesizing ATP, the mitochondrial Fo/F1 ATPase, for the cell's energy requirements. It's just a small example of changes in genes (duplications and splicing events) that can encode for new proteins with unique functions from pre-existing genes encoding proteins with completely different functions and localization signals. I can't give away too much information at this point, but we'll be publishing something within in the next year if all the planned experiments, some currently under investigation, support our hypothesis that a particular cell adhesion protein interacts with this protein in these essential morphogenetic events. Given our understanding of how genetics works, it is not unreasonable to make an inference that some organisms had speciated because of an ability to produce new "mosaic" proteins made of parts of other proteins serving different functions..
I am often amazed at how much more capability and enthusiasm for science there is among elementary school youngsters than among college students.