Antibody to mannose 6-phosphate specific receptor induces receptor deficiency in human fibroblasts.
Polyclonal antibodies to the mannose 6-phosphate specific receptor from human liver inhibited the endocytosis of lysosomal enzymes in fibroblasts by greater than 95% and enhanced 3-20-fold the secretion of precursors of lysosomal enzymes in these cells. Exposing fibroblasts for 4 h to antibody resulted in loss of greater than 90% of the membrane-bound receptors. If fibroblasts were treated with the antibody in the presence of CBZ-Phe-Ala-CHN2, an inhibitor of lysosomal cysteine proteinases, the receptor and smaller degradation products are recovered in dense lysosomes. In treated cells 18-58% of total receptor-related polypeptides were recovered in dense lysosomes. In control cells less than 4% of the receptor was found in the lysosomal fraction. We conclude from these results that normally the receptor is spared from lysosomal degradation. When tagged with antibody, however, the receptor is transported into lysosomes and degraded. The loss of intracellular receptors involved in segregation of newly synthesized lysosomal enzymes indicates an exchange between the former and the plasma membrane-bound receptors.
D000818:Animals; D000906:Antibodies; D002478:Cells, Cultured; D004705:Endocytosis; D005347:Fibroblasts / Q000378:metabolism; D006600:Hexosephosphates / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008360:Mannosephosphates / Q000378:metabolism*; D051381:Rats; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
D000906:Antibodies; D006600:Hexosephosphates; D008360:Mannosephosphates; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface