权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Sugar chains of lysosomal enzymes and sphingolipid activator proteins, and the relationship with their transport mechanism

溶酶体酶和鞘脂激活蛋白的糖链及其转运机制的关系

基本信息

批准号：
62580123
负责人：
YAMASHITA Katsuko
金额：
$ 1.09万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

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.

溶酶体中许多鞘脂的酶降解是由称为鞘脂激活蛋白SAP-1、SAP-2和SAP-3的小（8至13 kD）糖蛋白刺激的。由于这些激活剂在生物合成后被转运到溶酶体中，它们与天冬酰胺相连的糖链应该作为溶酶体的交通信号。为了阐明SAPs与溶酶体的运输机制以及酸性糖苷酶在溶酶体降解糖蛋白糖链中的作用，我们研究了从正常人肝脏和GM1神经节脂质病、1型、肝脏、豚鼠肾脏和戈谢病脾脏中纯化的SAR-1释放的糖链结构。削弱了除了SAP-1纯化的糖链GM1 gangliosidosis肝脏是彼此平等的定性和结构以下八个部分:1 6(1人3)1人4 GlcNAc 1 4 (Fuc 1 6) GlcNAc, 1 6 1 4 GlcNAc 1 4人(Fuc 1 6) GlcNAc, 1 4 1 4 GlcNAc 1 4人(Fuc 1 6) GlcNAc, GlcNAc 1 4 GlcNAc GlcNAc,表明糖链lysosoms中的本机削弱了被exoglycosidases sequencially退化。似乎很难推测从正常器官中纯化的天然蛋白如SAP-1的糖链在运输机制中的作用。而从GM1神经节神经节病（1型）肝脏中纯化的SAP-1糖链中有15%含有唾液化的单至四天线寡糖，其余85%为中性的单、双、三和四天线复合物型糖链，其中含有聚焦化和非聚焦化的三甲酰基核，以及外链上的n -乙酰乳胺基，尽管它们被轻微降解。这些结果表明，一些复杂类型的糖链，包括n -乙酰乳胺基团、与近端n -乙酰氨基葡萄糖胺相连的焦酰基残基和唾液酸等，可能作为交通信号，将SAP-1从高尔基体运输到溶酶体。