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

Christina Zachos, Judith Blanz, Paul Saftig, Michael Schwake*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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 languageEnglish (US)
Pages (from-to)1113-1123
Number of pages11
JournalTraffic
Volume13
Issue number8
DOIs
StatePublished - 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

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Fingerprint

Dive into the research topics of 'A Critical Histidine Residue Within LIMP-2 Mediates pH Sensitive Binding to Its Ligand β-Glucocerebrosidase'. Together they form a unique fingerprint.

Cite this