Binding and transport of gangliosides by prosaposin.

Abstract

Prosaposin, the precursor of saposins A, B, C, and D, which activate lysosomal hydrolysis of sphingolipids, exists in various tissues and body fluids and is especially abundant in the nervous system. Prosaposin and saposins A,B, C, and D formed stable complexes with 13 different gangliosides as measured by an assay using column chromatography. Gangliosides of the gangliotetraose type (a series) were bound with high affinity, whereas b series gangliosides, O-acetylated gangliosides, and gangliosides with shorter carbohydrate chains, were bound with lower affinity. Prosaposin and saposins transferred gangliosides from donor liposomes to erythrocyte ghost membranes. Prosaposin also stimulated ganglioside GM1 beta-galactosidase more than mature saposins. Prosaposin exists as a secretory protein and as an integral membrane protein, and we propose that prosaposin is active as a ganglioside binding and transport protein in vivo.