Lysosomal integral membrane protein type-2 (LIMP-2/SCARB2) is a substrate of cathepsin-F, a cysteine protease mutated in type-B-Kufs-disease
Judith Peters, Andrea Rittger, Rebecca Weisner, Johannes Knabbe, Friederike Zunke, Michelle Rothaug, Markus Damme, Samuel F Berkovic, Judith Blanz, Paul Saftig, Michael Schwake
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2015
The lysosomal integral membrane protein type-2 (LIMP-2/SCARB2) has been identified as a receptor for enterovirus 71 uptake and mannose-6-phosphate-independent lysosomal trafficking of the acid hydrolase β-glucocerebrosidase. Here we show that LIMP-2 undergoes proteolytic cleavage mediated by lysosomal cysteine proteases. Heterologous expression and in vitro studies suggest that cathepsin-F is mainly responsible for the lysosomal processing of wild-type LIMP-2. Furthermore, examination of purified lysosomes revealed that LIMP-2 undergoes proteolysis in vivo. Mutations in the gene encoding cathepsin-F (CTSF) have recently been associated with type-B-Kufs-disease, an adult form of neuronal cero..View full abstract
Awarded by Research Training Group of the Deutsche Forschungsgemeinschaft (DFG)
We thank Lisa Andresen and Maike Langer for excellent technical support. This work was supported by the Research Training Group (GRK 1459) of the Deutsche Forschungsgemeinschaft (DFG) to JB and MS and a Boehringer Ingelheim grant to FZ.