The eukaryotic cell is divided in functional compartments. One of these membrane-bound organelles is the lysosome where a set of more than 50 specialized enzymes are responsible for the breakdown of macromolecules like proteins, complex lipids and oligosaccharides. The final products of the digestion of macromolecules are re-utilized by the cell so that the lysosome functions as a recycling centre of the cell. Lysosomal proteins are transported towards the lysosomal compartment via the ER and Golgi apparatus and often undergo complex modification events like glycosylation and proteolytic processing during their course of activation. A group of ~ 40 genetic disorders, called lysosomal storage diseases, are caused by defects in one or more of the lysosomal enzymes and are characterized by massive accumulation of undigested substrates inside the lysosome leading to severe clinical symptoms or even to death.
We are interested in the identification and characterization of novel lysosomal proteins as well as in the characterization of pathological cascades in mouse models for lysosomal storage diseases.
2D-DIGE of lysosomal proteins from wild-type (WT, green) and α-mannosidosis mice (α-Man,red) (Damme et al., 2010)