A Critical Histidine Residue Within LIMP-2 Mediates pH Sensitive Binding to Its Ligand beta-Glucocerebrosidase

作者：Zachos Christina; Blanz Judith; Saftig Paul; Schwake Michael^*

来源：Traffic, 2012, 13(8): 1113-1123.

DOI：10.1111/j.1600-0854.2012.01372.x

• ss-glucocerebrosidase
• action myoclonus-renal failure syndrome
• Gaucher disease
• LIMP-2
• lysosomal transport
• lysosomes
• progressive myoclonus epilepsy
• SCARB2

The lysosomal membrane protein type 2 is a novel identified lysosomal sorting receptor for beta-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.

• 出版日期2012-8