GM1-gangliosidosis. Defective recognition site on beta-galactosidase precursor.
Cultured fibroblasts from different variants of GM1-gangliosidosis synthesize normal amounts of 88-kDa beta-galactosidase precursor. Yet the amount of the mature 64-kDa form is reduced to 5-15% of normal values. In this communication it is shown that the mutation in the infantile and adult form of GM1-gangliosidosis interferes with the phosphorylation of precursor beta-galactosidase. As a result the precursor is secreted instead of being compartmentalized into the lysosomes and further processed. The impaired phosphorylation might be due to conformational changes of the precursor molecule.
D002478:Cells, Cultured; D004792:Enzyme Precursors / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000378:metabolism*; D005696:Galactosidases / Q000235:genetics*; D005733:Gangliosidoses / Q000201:enzymology*; D006801:Humans; D008970:Molecular Weight; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012867:Skin / Q000201:enzymology; D001616:beta-Galactosidase / Q000235:genetics* / Q000302:isolation & purification
D004792:Enzyme Precursors; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D005677:G(M1) Ganglioside; D005696:Galactosidases; D001616:beta-Galactosidase