Recombinant GM2-activator protein stimulates in vivo degradation of GA2 in GM2 gangliosidosis AB variant fibroblasts but exhibits no detectable binding of GA2 in an in vitro assay.
The interaction between glycosphingolipids and recombinant human GM2-activator was studied in a microwell binding assay. A-series gangliosides like GM3, GM2 and GM1 were strongly bound by the recombinant human GM2 activator. A weak binding was observed to GD1b and sulfatide, while neutral glycolipids were not bound. Optimal binding occurred at pH 4.2 and was inhibited by increasing concentrations of citrate buffer and NaCl. In contrast with these in vitro results the recombinant human GM2-activator is able to restore the degradation of GA2 in fibroblasts from patients with the AB variant of GM2 gangliosidosis in vivo.
Bierfreund
U
U
Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Germany.
Lemm
T
T
Hoffmann
A
A
Uhlhorn-Dierks
G
G
Childs
R A
RA
Yuen
C T
CT
Feizi
T
T
Sandhoff
K
K
D001710:Biotin / Q000378:metabolism; D002478:Cells, Cultured; D002951:Citrates; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D049289:G(M2) Activator Protein; D005732:Gangliosides; D005733:Gangliosidoses; D006028:Glycosphingolipids / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007223:Infant; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012497:Sandhoff Disease / Q000378:metabolism*; D012965:Sodium Chloride; D013661:Tay-Sachs Disease / Q000378:metabolism*