The protective protein : a multifunctional lysosomal enzyme

This thesis describes the characterization of a lysosomal protein, the 'protective protein', that has at least two functions. On the one hand it protects lysosomal ~galactosidase and neuraminidase from degradation within the lysosome, hence its name. On the other hand it has peptidase and deamidase activities, that could be involved in protein turnover in lysosomes and hormone (in)activation. Degradation is distinguished here from proteolytic processing, although both involve peptide hydrolysis. The first is, however, an aspecific random process, carried out at multiple sites, whereas the second is a highly specific (single) event. Given the putative function of the protective protein it seemed appropriate to start with an overview of intracellular sites of protein degradation, followed by a section on the biogenesis of lysosomes. The introduction ends with a summary on what is known about lysosomal storage disorders, a group of genetic diseases that are due to defects in lysosomal proteins. The protective protein itself is impaired in the rare disorder galactosialidosis and studies on this disease have been the basis for the discovery of the protein and analysis of its functions.