Glycosphingolipidsare important constituents of cellular membranes. Glucosylceramide (GlcCer) is the simplest glycosphingolipid and serves as a building block for the synthesis of higher-order glycosphingolipids. Defects in the lysosomal beta-glucosidase 1 (GBA1), which cleaves GlcCer to glucose and ceramide, causes accumulation ofGlcCer in lysosomes and, thereby, the severe lipid-storage disorder Gaucher disease.
The function of GBA2 has been elusive for many years. Knockout-mice lacking the non-lysosomal beta-glucosidase 2 (GBA2) accumulate GlcCer outside the lysosomes. The main phenotype of GBA2 knockout-mice is male infertility due to a defect during sperm development.
We aim to nvestigate the molecular mechanism how glucosylceramide controls signaling pathways not only during sperm development, but also in other cell types and subcellular compartments.
Deutsche Forschungsgemeinschaft (DFG)