Lysosomal enzyme inactivation associated with defects in post-translational modification during development in Dictyostelium discoideum.
The developmental accumulation of lysosomal alpha-mannosidase-1 activity in Dictyostelium discoideum is controlled at the level of de novo enzyme precursor biosynthesis. Aggregation-deficient mutants are defective with regard to the accumulation of alpha-mannosidase-1 activity beyond 8-16 h of development. We used enzyme-specific monoclonal antibodies to show that the activity defect in aggregation-deficient strains is not due to a lack of alpha-mannosidase-1-precursor synthesis or processing, or to preferential degradation of the mature enzyme protein. Instead, the defect is a result of enzyme inactivation: cells of aggregation-deficient strains contain significant amounts of inactive alpha-mannosidase-1 protein late in development. The alpha-mannosidase-1 inactivation phenotype is associated with a more general defect in lysosomal enzyme modification. A change in the post-translational modification system occurs during normal slime-mold development, as shown by differences in enzyme isoelectric point, antigenicity, and thermolability. We found that this change in modification does not occur in mutant strains blocked early in development. We propose a model in which pleiotropic mutations in early aggregation-essential genes can indirectly affect the accumulation of alpha-mannosidase-1 activity by preventing the expression of a developmentally controlled change in the post-translational modification system, a change which is required for the stability of several lysosomal enzymes late in development.
D004789:Enzyme Activation; D008247:Lysosomes / Q000201:enzymology* / Q000378:metabolism; D008361:Mannosidases / Q000096:biosynthesis / Q000378:metabolism*; D009154:Mutation; D009235:Myxomycetes / Q000201:enzymology / Q000235:genetics / Q000254:growth & development*; D010447:Peptide Hydrolases; D011499:Protein Processing, Post-Translational; D043323:alpha-Mannosidase
D008361:Mannosidases; D043323:alpha-Mannosidase; D010447:Peptide Hydrolases