Lysosomal integral membrane protein type-2 (LIMP-2/SCARB2) is a substrate of cathepsin-F, a cysteine protease mutated in type-B-Kufs-disease.

Abstract

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 ceroid-lipofuscinosis. In this study we show that disease-causing cathepsin-F mutants fail to cleave LIMP-2. Our findings provide evidence that LIMP-2 represents an in vivo substrate of cathepsin-F with relevance for understanding the pathophysiology of type-B-Kufs-disease.

• Authors: Judith Peters, Andrea Rittger, Rebecca Weisner, Johannes Knabbe, Friederike Zunke, Michelle Rothaug, Markus Damme, Samuel F Berkovic, Judith Blanz, Paul Saftig, Michael Schwake
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 457 Issue 3 Pg. 334-40 (Feb 13 2015) ISSN: 1090-2104 [Electronic] United States
• PMID: 25576872 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• CD36 Antigens
• Lysosome-Associated Membrane Glycoproteins
• Mutant Proteins
• Receptors, Scavenger
• Recombinant Proteins
• SCARB2 protein, human
• Scarb2 protein, mouse
• CTSF protein, human
• Cathepsin F
• Ctsf protein, mouse

Topics

• Animals
• CD36 Antigens (chemistry, genetics, metabolism)
• Cathepsin F (genetics, metabolism)
• Cell Line
• HEK293 Cells
• Humans
• Lysosome-Associated Membrane Glycoproteins (chemistry, genetics, metabolism)
• Lysosomes (metabolism)
• Mice
• Models, Molecular
• Mutant Proteins (genetics, metabolism)
• Neuronal Ceroid-Lipofuscinoses (genetics, metabolism)
• Protein Conformation
• Protein Structure, Secondary
• Proteolysis
• Receptors, Scavenger (chemistry, genetics, metabolism)
• Recombinant Proteins (genetics, metabolism)
• Substrate Specificity