Neither type of mannose 6-phosphate receptor is sufficient for targeting of lysosomal enzymes along intracellular routes.
Mouse embryonic fibroblasts that are deficient in the two mannose 6-phosphate receptors (MPRs) MPR 46 and MPR 300 missort the majority (> or = 85%) of soluble lysosomal proteins into the medium. Human MPR 46 and MPR 300 were expressed in these cells to test whether overexpression of a single type of MPR can restore transport of lysosomal proteins to lysosomes. Only a partial correction of the missorting was observed after overexpression of MPR 46. Even at MPR 46 levels that are five times higher than the wild-type level, more than one third of the newly synthesized lysosomal proteins accumulates in the secretions. Two-fold overexpression of MPR 300 completely corrects the missorting of lysosomal enzymes. However, at least one fourth of the lysosomal enzymes are transported along a secretion-recapture pathway that is sensitive to mannose 6-phosphate in medium. In control fibroblasts that express both types of MPR, the secretion-recapture pathway is of minor importance. These results imply that neither overexpression of MPR 46 nor MPR 300 is sufficient for targeting of lysosomal proteins along intracellular routes.
Kasper
D
D
Georg-August-University, Abt. Biochemie II, Göttingen, Germany.
Dittmer
F
F
von Figura
K
K
Pohlmann
R
R
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001692:Biological Transport; D002402:Cathepsin D / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D002461:Cell Line, Transformed; D005347:Fibroblasts; D006026:Glycoside Hydrolases / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000201:enzymology*; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D009154:Mutation; D011506:Proteins / Q000378:metabolism*; D017527:Receptor, IGF Type 2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins; D014162:Transfection
D015703:Antigens, CD; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D011506:Proteins; D017527:Receptor, IGF Type 2; D011994:Recombinant Proteins; C018589:lysosomal proteins; D006026:Glycoside Hydrolases; D002402:Cathepsin D