Recombinant GM2-activator protein stimulates in vivo degradation of GA2 inGM2 gangliosidosis AB variant fibroblasts but exhibits no detectable binding of GA2 in an in vitro assay

The interaction between glycosphingolipids and recombinant human GM2-activa tor was studied in a microwell binding assay. A-series gangliosides like GM 3, GM2 and GM1 were strongly bound by the recombinant human GM2 activator. A weak binding was observed to GD1b and sulfatide, while neutral glycolipid s were not bound. Optimal binding occurred at pH 4.2 and was inhibited by i ncreasing concentrations of citrate buffer and NaCl. In contrast with these in vitro results the recombinant human GM2-activator is able to restore th e degradation of GA2 in fibroblasts from patients with the AB variant of GM 2 gangliosidosis in vivo.