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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)334-340
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume457
Issue number3
DOIs
StatePublished - Feb 13 2015

Keywords

  • Cathepsin-F
  • Kufs disease
  • LIMP-2
  • Lysosomal storage disease
  • Neuronal ceroid-lipofuscinosis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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