The mannose receptor and the cation-dependent form of mannose 6-phosphate receptor have overlapping cellular and subcellular distributions in liver.
The trafficking of newly synthesized lysosomal enzymes is mediated by two distinct mannose 6-phosphate receptors (MPRs). These receptors have been shown previously to have nonidentical distributions among subcellular fractions purified from bovine liver [D. J. Messner et al. (1989) J. Cell Biol. 108, 2149-2162]. In that study, a 170-kDa protein was discovered to be strikingly enriched in a subclass of bovine liver membranes containing the 46-kDa cation-dependent MPR (CD-MPR). The identity and distribution of this protein are described in the present study. The apparent size, extent of glycosylation, and amino-terminal amino acid sequence (XXTRPFLIYNED) of the 170K protein suggest it is the mannose receptor, a cell-type specific protein present at high levels in liver sinusoidal cells (but not hepatocytes). This identification was confirmed by demonstrating that the 170K protein can bind to mannose affinity columns. Antibodies specific for the 170K protein/mannose receptor were generated and purified using a synthetic peptide corresponding to its N-terminal sequence. Western blotting with the anti-170K peptide antibodies indicate the mannose receptor is highly enriched in membrane fractions immunoisolated with antibodies to the CD-MPR, but less enriched (by several-fold) in fractions obtained with antibodies specific for the 270-kDa insulin-like growth factor II/cation-independent MPR (IGF-II/CI-MPR). A differential overlap between the mannose receptor and the MPRs can also be detected by indirect immunofluorescence of bovine liver sections. These observations indicate that mannose receptor-enriched membranes of liver sinusoidal cells contain significant levels of the CD-MPR, but not the IGF-II/CI-MPR.
Messner
D J
DJ
Department of Pharmacology, University of Rochester Medical Center, New York 14642.
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D002417:Cattle; D005455:Fluorescent Antibody Technique; D006801:Humans; D037181:Lectins, C-Type; D008099:Liver / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D008358:Mannose / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D017527:Receptor, IGF Type 2 / Q000032:analysis* / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000737:chemistry
D000906:Antibodies; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009842:Oligopeptides; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; D008358:Mannose