Abstract
The lysosomal membrane protein type 2 is a novel identified lysosomal sorting receptor for β-glucocerebrosidase (GC). Mutations in both genes underlie human pathologies causing action myoclonus-renal failure syndrome (AMRF) and Gaucher disease (GD), respectively. We now demonstrate that the lumenal acidification mediated by the vacuolar (H+)-ATPase triggers the dissociation of LIMP-2 and GC in late endosomal/lysosomal compartments. Moreover, we identified a single histidine residue in LIMP-2 that is necessary for LIMP-2 and GC binding. This residue is in close proximity to a proposed coiled-coil domain, which determines the binding to GC and may function as a critical pH sensor.
Original language | English (US) |
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Pages (from-to) | 1113-1123 |
Number of pages | 11 |
Journal | Traffic |
Volume | 13 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2012 |
Keywords
- Action myoclonus-renal failure syndrome
- Gaucher disease
- LIMP-2
- Lysosomal transport
- Lysosomes
- Progressive myoclonus epilepsy
- SCARB2
- β-glucocerebrosidase
ASJC Scopus subject areas
- Genetics
- Molecular Biology
- Structural Biology
- Biochemistry
- Cell Biology