| Research Abstract |
The enzymatic degradation of a number of sphingolipids in the lysosomes is stimulated by small (8 to 13 kD) glycoproteins named sphingolipid activator proteins SAP-1, SAP-2, and SAP-3. Since these activators are translocated into lysosomes after biosynthesis, their asparagine-linked sugar chains should act as a traffic signal to lysosomes.
In order to elucidate the traffic mechanism of SAPs to the lysosome and the role of acid glycosidases in lysosomal degradation of sugar chains of glycoproteins, we have investigated the structures of sugar chains released from SAR-1 purified from normal human liver and GM1 gangliosidosis, Type 1, liver, guinea pig kidnney SAP-3, and Gaucher disease spleen SAP-2. The sugar chains of SAPs except SAP-1 purified from GM1 gangliosidosis liver were equal qualitatively with one another and their structures were the following eight components: Man 1 6(Man 1 3)Man 1 4GlcNAc 1 4( Fuc 1 6)GlcNAc, Man 1 6Man 1 4GlcNAc 1 4( Fuc 1 6) GlcNAc, Man 1 4Man 1 4GlcNAc 1 4( Fuc 1 6)GlcNAc, GlcNAc 1 4GlcNAc, and GlcNAc, indicating that sugar chains of native SAPs were degraded sequencially by exoglycosidases in lysosoms. It seems difficult to speculate the role in the transport mechanism of those suger chains of the native protein like SAP-1 purified from the normal organs.
While,fifteen percent of the sugar chains of SAP-1 purified from liver of GM1 gangliosi-dosis, Type 1, contained sialylated mono- to tetra-antennary oligosaccharides and the remaining 85 % was neutral mono-, bi-, tri-, and tetra- antennary complex type sugar chains containing fucosylated and nonfucosylated trimannosyl cores, and N-acetyllactosamine groups at outer chains, although they are slightly degraded. These results indicate that some complex type sugar chains including N-acetyllactosamine group, the fucosyl residue linked to the proximal N-acetylglucosamine, and the sialic acid et al. may act as a traffic signal to transport SAP-1 from the golgi apparatus to the lysosome.
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