Adult forms of glycogenosis type II

Reuser, Arnold; Kroos, Marian A.

doi:10.1016/0014-5793(82)80953-8

Cited by 29 publications

(4 citation statements)

References 8 publications

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“…Analogous results have been described in [19]; fibroblasts were cultured in the presence of NH&l and measured acid cu-glucosidase activity in the medium; the rate of appearance of the activity in the medium in mutant fibroblasts was -10% of that in control fibroblasts. The reduced secretion of newly synthesized aglucosidase in adult Pompe fibroblasts was not due to retention of the enzyme in the cells; in the presence of 10 mM NH&l, the same proportion of newly synthesized a-gluosidase (-50070) was found intracellularly in control fibroblasts (see also [l 11) as in adult Pompe fibroblasts.…”

Section: Resultssupporting

confidence: 78%

“…The stability of acid a-glucosidase in lysosomes has been estimated by allowing purified enzyme to be endocytosed by fibroblasts from patients with the infantile form of Pompe's disease and monitoring the enzyme activity in the cells [ 191. aGlucosidase purified from fibroblasts from patients with the late-onset form of Pompe's disease had about the same half-life as that from secretions of control fibroblasts [19].…”

Section: Resultsmentioning

confidence: 95%

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Biosynthesis of acid α‐glucosidase in late‐onset forms of glycogenosis type II (Pompe's disease)

et al. 1982

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Cultured human skin fibroblasts from control persons and from patients with the generalized and lateonset forms of Pompe's disease were labelled with radioactive leucine and the incorporation of radioactivity into acid cY-glucosidase and cathepsin D was analysed by immunoprecipitation, gel electrophoresis and fluorography. When the labelling was carried out for 6-12 h in the presence of NH&l, the labelling of secreted cu-glucosidase relative to that of secreted cathepsin D in fibroblasts from patients with the lateonset form of Pompe's disease was < 15% of that in fibroblasts from control persons. However, when the fibroblasts were labelled for < 1 h, the relative rate of incorporation of radioactivity into acid a-glucosidase was rather similar in the two types of fibroblasts. In fibroblasts from patients with the generalized form of Pompe's disease no incorporation of radioactivity into acid cy-glucosidase could be detected.

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Section: Resultssupporting

confidence: 78%

Section: Resultsmentioning

confidence: 95%

Biosynthesis of acid α‐glucosidase in late‐onset forms of glycogenosis type II (Pompe's disease)

et al. 1982

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“…Enzyme deficiency leads to glycogenosis type II, an inherited glycogen-storage disorder (Hers, 1963). Several patients have been described with a defect in the synthesis or post-translational processing of lysosomal a-glucosidase (Reuser and Kroos, 1982;Beratis et al, 1983;Reuser et al, 1985Reuser et al, , 1987Martiniuk et al, 1986Martiniuk et al, , 1990aVan der Ploeg et al, 1989;Hermans et al, 1991a;Zhong et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Human lysosomal α-glucosidase: functional characterization of the glycosylation sites

Hermans

Wisselaar

Kroos

et al. 1993

Biochemical Journal

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N-linked glycosylation is one of the important events in the post-translational modification of human lysosomal alpha-glucosidase. Phosphorylation of mannose residues ensures efficient transport of the enzyme to the lysosomes via the mannose 6-phosphate receptor. The primary structure of lysosomal alpha-glucosidase, as deduced from the cDNA sequence, indicates that there are seven potential glycosylation sites. We have eliminated these sites individually by site-directed mutagenesis and thereby demonstrated that all seven sites are glycosylated. The sites at Asn-882 and Asn-925 were found to be located in a C-terminal propeptide which is cleaved off during maturation. Evidence is presented that at least two of the oligosaccharide side chains of human lysosomal alpha-glucosidase are phosphorylated. Elimination of six of the seven sites does not disturb enzyme synthesis or function. However, removal of the second glycosylation site at Asn-233 interferes dramatically with the formation of mature enzyme. The mutant precursor is synthesized normally and assembles in the endoplasmic reticulum, but immunoelectron microscopy reveals a deficiency of alpha-glucosidase in the Golgi complex and in the more distal compartments of the lysosomal transport pathway.

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“…Apart from clinical heterogeneity, there is also a high degree of biochemical and molecular heterogeneity. A multitude of mutant alleles has been suspected from the molecular abnormalities of the lysosomal a-glucosidase species in cultured fibroblasts and muscle cells from several patients (Reuser et al, 1978(Reuser et al, , 1985(Reuser et al, , 1987Beratis et al, 1978Beratis et al, , 1983; Reuser and Kroos, 1982;Van der Ploeg et al, 1989;Hoefsloot et al, 1990a). Genetic heterogeneity has been demonstrated more directly by Southernand Northern-blot analysis (Martiniuk et al, 1986(Martiniuk et al, , 1990aHoefsloot et al, 1988;Reuser et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

The conservative substitution Asp-645→Glu in lysosomal α-glucosidase affects transport and phosphorylation of the enzyme in an adult patient with glycogen-storage disease type II

Hermans

Graaff

Kroos

et al. 1993

Biochemical Journal

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Glycogen-storage disease type II (GSDII) is caused by the deficiency of lysosomal alpha-glucosidase (acid maltase). This paper reports on the analysis of the mutant alleles in an American black patient with an adult form of GSDII (GM1935). The lysosomal alpha-glucosidase precursor of this patient has abnormal molecular features: (i) the molecular mass is decreased, (ii) the phosphorylation is deficient and (iii) the proteolytic processing is impaired. Sequence analysis revealed four mutations leading to amino acid alterations: Asp-645-->Glu, Val-816-->Ile, Arg-854-->Stop and Thr-927-->Ile. By using allele-specific oligonucleotide hybridization on PCR-amplified cDNA we have demonstrated that the Arg-854-->Stop mutation is located in one allele that is not expressed, and that the other allele contains the remaining three mutations. Each of the mutations was introduced in wild-type cDNA and expressed in COS cells to analyse the effect on biosynthesis, transport and phosphorylation of lysosomal alpha-glucosidase. The Val-816-->Ile substitution appeared to have no significant effect in contrast with results [Martiniuk, Mehler, Bodkin, Tzall, Hirshhorn, Zhong and Hirschhorn (1991) DNA Cell Biol. 10, 681-687] and was therefore defined as a polymorphism. The Thr-927-->Ile substitution deleting one of the seven glycosylation sites was found to be responsible for the decrease in molecular-mass, but not for the deficient proteolytic processing and phosphorylation. It did not cause the enzyme deficiency either. The third mutation leading to the Asp-645-->Glu substitution was proven to account in full for the observed defects in transport, phosphorylation and proteolytic processing of the newly synthesized alpha-glucosidase precursor of the patient.

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Adult forms of glycogenosis type II

Cited by 29 publications

References 8 publications

Biosynthesis of acid α‐glucosidase in late‐onset forms of glycogenosis type II (Pompe's disease)

Biosynthesis of acid α‐glucosidase in late‐onset forms of glycogenosis type II (Pompe's disease)

Human lysosomal α-glucosidase: functional characterization of the glycosylation sites

The conservative substitution Asp-645→Glu in lysosomal α-glucosidase affects transport and phosphorylation of the enzyme in an adult patient with glycogen-storage disease type II

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