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

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 lysosom...

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Main Authors: Peters, Judith (Author) , Rittger, Andrea (Author) , Weisner, Rebecca (Author) , Knabbe, Johannes (Author) , Zunke, Friederike (Author) , Rothaug, Michelle (Author) , Damme, Markus (Author) , Berkovic, Samuel F. (Author) , Blanz, Judith (Author) , Saftig, Paul (Author) , Schwake, Michael (Author)
Format: Article (Journal)
Language:English
Published: 7 January 2015
In: Biochemical and biophysical research communications
Year: 2015, Volume: 457, Issue: 3, Pages: 334-340
ISSN:1090-2104
DOI:10.1016/j.bbrc.2014.12.111
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.bbrc.2014.12.111
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0006291X14023250
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Author Notes:Judith Peters, Andrea Rittger, Rebecca Weisner, Johannes Knabbe, Friederike Zunke, Michelle Rothaug, Markus Damme, Samuel F. Berkovic, Judith Blanz, Paul Saftig, Michael Schwake
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Summary: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.
Item Description:Gesehen am 11.02.2021
Physical Description:Online Resource
ISSN:1090-2104
DOI:10.1016/j.bbrc.2014.12.111

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