Lysosomal Membrane Glycoproteins
Lysosomal Membrane Glycoproteins
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溶酶体膜糖蛋白
DOI：
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发表时间：
2001
期刊：
影响因子：
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通讯作者：
M. Fukuda
中科院分区：
文献类型：
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作者：
M. Fukuda
溶酶体是哺乳动物细胞的主要消化区室。它们负责降解内吞作用内化的外来物质和自噬作用期间递送至溶酶体的细胞内物质（1，2）。在过去的几年里，在理解溶酶体酶的生物合成和靶向方面取得了重大进展，研究结果可以总结如下（综述见参考文献10）。第3和第4段）。新合成的溶酶体酸水解酶上的天冬酰胺连接的高甘露糖寡糖在高尔基体中获得磷酸基团。然后，所得的甘露糖6-磷酸基团作为溶酶体酶与位于高尔基体中的甘露糖6-磷酸受体结合的特异性识别标记。受体-溶酶体酶复合物易位至前溶酶体区室，在此复合物通过低pH（pH 5.5）解离。溶酶体酶被连续地包装到溶酶体中，而甘露糖6磷酸受体再循环回到高尔基体。一些甘露糖6-磷酸受体到达细胞表面，然后可以通过内吞途径将溶酶体酶从细胞表面递送到溶酶体。与溶酶体酸水解酶的广泛知识相反，对溶酶体膜的组分知之甚少。溶酶体膜通过将大量的酸性水解酶与其余的细胞质组分隔离，在溶酶体的正常功能中起着至关重要的作用。溶酶体膜可能参与溶酶体的各种重要功能，例如其对溶酶体水解酶降解的抗性及其与其他膜细胞器（包括内体、吞噬体和质膜）特异性相互作用和融合的能力。溶酶体膜还维持酸性溶酶体内环境，并转运由溶酶体水解酶产生的氨基酸和单糖和寡糖（综述见参考文献1）。第1-3段）。为了了解溶酶体膜的组分，最初尝试鉴定溶酶体膜蛋白，其是溶酶体特有的并且不存在于质膜中。伯恩赛德和施耐德（5）以及大隅等人（6）鉴定了两种这样的糖蛋白：M为-60，000的糖蛋白和M为-90，000-110，000的糖蛋白。然而，其他的研究是通过产生抗纯化的溶酶体膜的单克隆抗体来鉴定溶酶体膜糖蛋白。通过这种方法，Barriocanal等人（7）和刘易斯等人（8）鉴定了三组不同的溶酶体膜糖蛋白：M为-90，000-120，000的溶酶体膜糖蛋白; M为-72，000的溶酶体膜糖蛋白; M为-27，000的溶酶体膜糖蛋白。在这些糖蛋白中，M_1 ~ 90，000 - 120，000的糖蛋白被不同的工作者独立地发现为溶酶体膜的主要成分。首先，Chen等人（9）发现有两种不同的糖蛋白具有这些分子量，称为lamp-1和lamp-2，后者与Mac 3相同（10）。Lippincott-Schwartz和Fambrough（11）确定
Lysosomes serve as the major digestive compartment of mammalian cells. They are responsible for the degradation of foreign materials internalized by endocytosis and intracellular material delivered to lysosomes during autophagocytosis (1,2). In the past several years, significant progress has been made in understanding the biosynthesis and targeting of lysosomal enzymes, and the findings can be summarized as follows (for review see Refs. 3 and 4). Asparagine-linked high mannose oligosaccharides on newly synthesized lysosomal acid hydrolases acquire phosphate groups in the Golgi apparatus. The resulting mannose 6-phosphate groups then serve as a specific recognition marker for the binding of lysosomal enzymes to mannose 6-phosphate receptors located in the Golgi apparatus. The receptor-lysosomal enzyme complex is translocated to a prelysosomal compartment where the complex is dissociated by the low pH (pH 5.5). The lysosomal enzymes are continuously packed into lysosomes, whereas the mannose 6phosphate receptors recycle back to the Golgi apparatus. Some of the mannose 6-phosphate receptors reach the cell surface and can then deliver lysosomal enzymes from the cell surface to the lysosomes through the endocytic pathway. In contrast to the extensive knowledge of lysosomal acid hydrolases, much less is known about the components of lysosomal membranes. The lysosomal membrane plays a vital role in the proper function of lysosomes by sequestering numerous acid hydrolases from the rest of the cytoplasmic components. The lysosomal membrane is presumably involved in various important functions of the lysosomes, such as its resistance to degradation by lysosomal hydrolases and its ability to interact and fuse specifically with other membrane organelles, including endosomes, phagosomes, and plasma membranes. The lysosomal membrane also maintains an acidic intralysosomal environment and transports amino acids and monoand oligosaccharides produced by lysosomal hydrolases (for review, see Refs. 1-3). In order to understand the components of the lysosomal membrane, initial attempts were made to identify lysosomal membrane proteins which are unique to lysosomes and not present in the plasma membrane. Burnside and Schneider (5) and Ohsumi et al. (6) identified two of such glycoproteins: those with M , -60,000 and those with M, -90,000-110,000. Other studies, however, were directed to identify lysosomal membrane glycoproteins by producing monoclonal antibodies against purified lysosomal membrane. By this approach, Barriocanal et al. (7) and Lewis et al. (8) identified three different groups of lysosomal membrane glycoproteins: those with M, -90,000-120,000; those with M, -72,000; and those with M , -27,000. Among these, the glycoproteins with M , -90,000-120,000 were found independently by different workers as the major components of the lysosomal membranes. First, Chen et al. (9) found that there are two different glycoproteins with these molecular weights, termed lamp-1 and lamp-2, with the latter shown to be identical to Mac3 (10). Lippincott-Schwartz and Fambrough (11) identified