title: Identification and characterization of cells deficient in the mannose 6-phosphate receptor: evidence for an alternate pathway for lysosomal enzyme targeting.
abstract: Newly synthesized lysosomal enzymes acquire phosphomannosyl units, which allow binding of the enzymes to the mannose 6-phosphate receptor and subsequent translocation to lysosomes. In some cell types, this sequence of events is necessary for the delivery of these enzymes to lysosomes. Using a slime mold lysosomal hydrolase as a probe, we have identified three murine cell lines that lack the receptor and one line that contains very low (3%) receptor activity. Each of these lines synthesizes the mannose 6-phosphate recognition marker on its lysosomal enzymes, but, unlike cell lines with high levels of receptor, the cells accumulate oligosaccharides containing phosphomonoesters. The receptor-deficient lines possess high levels of intracellular acid hydrolase activity, which is contained in dense granules characteristic of lysosomes. The data suggest that intracellular mechanisms independent of the mannose 6-phosphate receptor must exist in some cells for the delivery of acid hydrolases to lysosomal organelles.
mesh_terms: D000818:Animals; D002451:Cell Compartmentation; D002478:Cells, Cultured; D006224:Cricetinae; D006600:Hexosephosphates / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology*; D008360:Mannosephosphates / Q000378:metabolism*; D051379:Mice; D009844:Oligosaccharides / Q000378:metabolism; D010766:Phosphorylation; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D006600:Hexosephosphates; D008360:Mannosephosphates; D009844:Oligosaccharides; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface