title: Intracellular transport of acid alpha-glucosidase in human fibroblasts: evidence for involvement of phosphomannosyl receptor-independent system.
abstract: Intracellular transport of two lysosomal enzymes, acid alpha-glucosidase and beta-hexosaminidase, was analyzed in human fibroblasts. The precursors of beta-hexosaminidase in normal fibroblasts were released from the membrane fraction by treatment with mannose 6-phosphate, but the precursor of alpha-glucosidase was not. Percoll density gradient centrifugation revealed a normal amount of acid alpha-glucosidase activity in heavy lysosomes in I-cell disease fibroblasts despite impaired maturation and defective phosphorylation, and beta-hexosaminidase activity was markedly reduced in lysosomes. It was concluded that the membrane-bound precursor of acid alpha-glucosidase is transported to lysosomes by a phosphomannosyl receptor-independent system although the enzyme lacks the recognition marker for the phosphomannosyl receptor and processing of an intermediate form to mature forms does not occur in this disease.
authors.affiliation: Division of Inherited Metabolic Disease, National Institute of Neuroscience, Tokyo.
authors.forename: A
authors.initials: A
authors.lastname: Tsuji
authors.forename: K
authors.initials: K
authors.lastname: Omura
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D002478:Cells, Cultured; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear; D012995:Solubility; D013347:Subcellular Fractions; D000520:alpha-Glucosidases / Q000378:metabolism*; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; C034304:cation-dependent mannose-6-phosphate receptor; D000520:alpha-Glucosidases; D001619:beta-N-Acetylhexosaminidases