A late developmental change in lysosomal enzyme sulfation specific to newly synthesized proteins in Dictyostelium discoideum.

During development in Dictyostelium discoideum, several lysosomal glycosidases undergo changes in post-translational modification that are thought to involve differences in the extent of sulfation or phosphorylation, and appear to be required for the maintenance of cellular enzyme activity late in development. We have used monoclonal antibodies specific to the lysosomal enzyme alpha-mannosidase-1 to study the major late (12 hr) developmental change in the modification system. Pulse-chase experiments performed both early and late in development reveal that the substrate for the late form of modification is restricted to newly synthesized alpha-mannosidase-1 precursor protein. We have identified one modification difference between the two developmentally distinct isozymes of alpha-mannosidase-1: 35SO4 pulse-chase data show that the newly synthesized "late" enzyme precursor is significantly undersulfated in comparison with the enzyme synthesized early in development. This apparent lack of sulfation is associated with the lack of acquisition of endoglycosidase H resistance. By contrast, an aggregation-deficient mutant, which is defective with regard to the accumulation of alpha-mannosidase-1 activity late in development, synthesizes the "early" sulfated form of the enzyme throughout development. We conclude that the late developmental change in post-translational modification specifically involves one of the biochemical steps in which the N-linked oligosaccharide side chains of the newly synthesized alpha-mannosidase-1 precursor are modified by sulfation.