1. The 46-kDa mannose 6-phosphate receptor does not depend on endosomal acidification for delivery of hydrolases to lysosomes
- Author
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Phuong Ton, Barbara Svoboda, Andrew Gannon, Lukas Mach, Regina Pohlmann, Olivia C. Probst, Werner Schuhmann, and Johannes Wieser
- Subjects
Glycosylation ,Endosome ,Hydrolases ,Cathepsin L ,Mannose ,Mannose 6-phosphate ,Endosomes ,Biology ,Cathepsin D ,Receptor, IGF Type 2 ,Cathepsin B ,chemistry.chemical_compound ,Mice ,Lysosome ,3T3-L1 Cells ,medicine ,Animals ,Humans ,Tissue Distribution ,Monensin ,Receptor ,Cells, Cultured ,Mice, Knockout ,Mannose 6-phosphate receptor ,Ionophores ,Cell Biology ,Hydrogen-Ion Concentration ,Cathepsins ,Cell biology ,Cysteine Endopeptidases ,Protein Transport ,medicine.anatomical_structure ,chemistry ,Biochemistry ,NIH 3T3 Cells ,Signal transduction ,Lysosomes ,Signal Transduction - Abstract
In mammalian cells, the mannose 6-phosphate receptor pathway accounts for the transport of most soluble acid hydrolases to lysosomes. It is believed that dissociation of mannose 6-phosphate receptors and their ligands is entirely driven by the acidic environment in endosomal compartments. Indeed, pH-perturbing substances such as ammonium chloride and monensin have been shown to inhibit lysosomal enzyme targeting in cells that express both known mannose 6-phosphate receptors. We now demonstrate that ammonium chloride and monensin exert modest effects on the intracellular retention of lysosomal hydrolases in murine cells that synthesize only the 46-kDa mannose 6-phosphate receptor. Neither ammonium chloride nor monensin induces changes to the subcellular localization of lysosomal hydrolases and the 46-kDa mannose 6-phosphate receptor in these cells. This suggests that endosomal dissociation of the receptor and its ligands still occurs in the presence of these agents. We conclude that the murine 46-kDa mannose 6-phosphate receptor has the capacity to deliver its cargo proteins to lysosomes even in the absence of endosomal acidification.
- Published
- 2006