Is movement of mannose 6-phosphate-specific receptor triggered by binding of lysosomal enzymes?
Mannose 6-phosphate-specific receptors with an apparent molecular mass of 215,000 are present in fibroblasts at the cell surface and in intracellular membranes. The cell surface receptors mediate endocytosis of exogenous lysosomal enzymes and exchange with the intracellular receptors, which function in the sorting of endogenous lysosomal enzymes. In the present study, several methods independent of receptor ligands were designed in order to examine the exchange of receptors under conditions where receptor-ligand complexes do not dissociate (weak bases and monensin) or where receptor-ligand complexes are not formed due to absence of endogenous ligands as a result of inhibition of protein synthesis. Weak bases and monensin reduce the concentration of receptors at the cell surface by 20-30% and free cell surface receptors were replaced by occupied receptors. The latter continued to be exchanged with internal ligand-occupied receptors and the rates of the exchange were similar to the control values. The exchange of receptors between the cell surface and internal membranes was also not affected when the receptor ligands were depleted from the transport compartments by treating the cells with cycloheximide for up to 10 h. We conclude from these results that movement of mannose 6-phosphate-specific receptors along the endocytosis and sorting pathways is constitutive and not triggered by binding or dissociation of ligands.
D000643:Ammonium Chloride / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002402:Cathepsin D / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology*; D008360:Mannosephosphates / Q000378:metabolism; D008985:Monensin / Q000494:pharmacology; D017527:Receptor, IGF Type 2
D002352:Carrier Proteins; D008360:Mannosephosphates; D017527:Receptor, IGF Type 2; D000643:Ammonium Chloride; C027693:mannose-6-phosphate; D002738:Chloroquine; D008985:Monensin; D003513:Cycloheximide; D002402:Cathepsin D