Acetylglucosamine Residues from Phosphorylated High Mannose Oligosaccharides of Lysosomal Enzymes”

We recently reported that the high mannose-type oligosaccharides of the biosynthetic intermediates of &glucuronidase contain phosphate groups in diester linkage between mannose residues and outer a-linked N-acetylglucosamine residues (Tabas, I., and Kornfeld, S. (1980) J. Bwl. C h m . 255, 6633-6639). We now describe an a-N-acetylglucosaminyl phosphodiesterase from rat liver that is capable of removing the N-acetylglucosamine residues, leaving phosphomonoester groups on the high mannose oligosaccharide units. This activity is greatly enriched in smooth membrane preparations. It can be distinguished from a lysosomal a-Nacetylglucosaminidase by several criteria, including subcellular localization and differential inhibition by amino sugars. In addition, human fibroblasts with mutations which lead to a deficiency of the lysosomal activity have normal levels of the a-N-acetylglucosaminyl phosphodiesterase. This enzyme may be involved in the “unmasking” of the phosphomannosyl recognition marker on newly synthesized acid hydrolases which could then direct the targeting of these enzymes to lysosomes.