title: Mistargeting of lysosomal enzymes in M(r) 46,000 mannose 6-phosphate receptor-deficient mice is compensated by carbohydrate-specific endocytotic receptors.
abstract: Targeted disruption of the M(r) 46,000 mannose 6-phosphate receptor (MPR 46) in mice is associated with normal levels of lysosomal enzymes in the circulation, while in MPR 46-deficient cells an increased secretion of lysosomal enzymes is apparent [Köster, A., Saftig, P., Matzner, U., von Figura, K., Peters, C. & Pohlmann, R. (1993) EMBO J. 12, 5219-5223]. This points to the existence of mechanisms that prevent or compensate for mistargeting of lysosomal enzymes in vivo. In the present study, we have injected inhibitors of three carbohydrate-specific endocytotic receptors into MPR 46-deficient and control mice. Inhibition of these receptors was associated with a pronounced increase of three lysosomal enzymes in the serum of MPR 46-deficient mice. These results clearly show that lysosomal enzymes are mistargeted in MPR 46-deficient mice and that carbohydrate-specific endocytotic receptors are part of the mechanisms that compensate for the mistargeting of lysosomal enzymes in MPR 46-deficient mice. Moreover, evidence was obtained that, also in control mice, the steady-state level of some lysosomal enzyme is controlled by these receptors.
authors.affiliation: Abt. Biochemie II, Georg-August-Universität Göttingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Köster
authors.forename: K
authors.initials: K
authors.lastname: von Figura
authors.forename: R
authors.initials: R
authors.lastname: Pohlmann
mesh_terms: D000818:Animals; D001192:Arylsulfatases / Q000378:metabolism*; D001212:Asialoglycoproteins / Q000378:metabolism*; D004705:Endocytosis; D005260:Female; D007457:Iodine Radioisotopes; D007700:Kinetics; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D008351:Mannans / Q000378:metabolism; D008360:Mannosephosphates / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009961:Orosomucoid / Q000031:analogs & derivatives* / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000235:genetics*; D012016:Reference Values; D001619:beta-N-Acetylhexosaminidases / Q000097:blood*
chemical_list: D001212:Asialoglycoproteins; D007457:Iodine Radioisotopes; D008351:Mannans; D008360:Mannosephosphates; D009961:Orosomucoid; D017527:Receptor, IGF Type 2; C017030:asialoorosomucoid; C027693:mannose-6-phosphate; D001192:Arylsulfatases; D001619:beta-N-Acetylhexosaminidases