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

Peters J, Rittger A, Weisner R, Knabbe J, Zunke F, Rothaug M, Damme M, Berkovic SF, Blanz J, Saftig P, Schwake M (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Biochemical and Biophysical Research Communications Elsevier

Book Volume: 457

Pages Range: 334-340

Journal Issue: 3

DOI: 10.1016/j.bbrc.2014.12.111

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 with CRIS profile

Friederike Zunke

Involved external institutions

Christian-Albrechts-Universität zu Kiel DE Germany (DE) Universität Bielefeld DE Germany (DE) The University of Melbourne AU Australia (AU)

How to cite

APA:

Peters, J., Rittger, A., Weisner, R., Knabbe, J., Zunke, F., Rothaug, M.,... Schwake, M. (2015). Lysosomal integral membrane protein type-2 (LIMP-2/SCARB2) is a substrate of cathepsin-F, a cysteine protease mutated in type-B-Kufs-disease. Biochemical and Biophysical Research Communications, 457(3), 334-340. https://doi.org/10.1016/j.bbrc.2014.12.111

MLA:

Peters, Judith, et al. "Lysosomal integral membrane protein type-2 (LIMP-2/SCARB2) is a substrate of cathepsin-F, a cysteine protease mutated in type-B-Kufs-disease." Biochemical and Biophysical Research Communications 457.3 (2015): 334-340.

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