基质与内膜英文讲义(编辑修改稿)

基质与内膜英文讲义(编辑修改稿)内容摘要：

Characteristics of Lysosomes ① Lysosome is a heterogenous anelle: Primary lysosomes Second lysosomes heterophagic autophagic Residual body Primary Lys. Second Lys ② Lysosomes contain plenty acid hydrolases that can digest every kind of biological molecule. the principal sites of intracellular digestion. Marker enzyme: acid phosphatase ③ Lysosome membrane: H+pumps: internal proton concentration is kept high by H+ATPase Glycosylated proteins: may protect the lysosome from selfdigestion. Transport proteins: transporting digested materials. Figure 1318 The low pH in lysosomes and endosomes. Proteins labeled with a pHsensitive fluorescent probe (fluorescein) and then endocytosed by cells can be used to measure the pH in endosomes and lysosomes. The different colors reflect the pH that the fluorescent probe encounters in these anelles. The pH in lysosomes (red) is about 5, while the pH in various types of endosomes (blue and green) ranges from to . (Courtesy of Fred Maxfield and Kenh Dunn.) B. The Functions of Lysosomes Lysosomes are involved in three major cell functions: ① phagocytosis。 ② autophagy。 ③ endocytosis. Primary lys fuse with either phagocytic or autophagic vesicles, forming residual bodies that either undergo exocytosis or are retained in the cell as lipofuscin granules. C. Lysosomes and Diseases Disorders resulting from defects in lysosomal function: ① Autolysis: A break or leak in the membrane of lys releases digestive enzymes into the cell which damages the surrounding tissues (Silicosis). ② Lysosomal storage diseases are due to the absence of one or more lysosomal enzymes, and resulting in accumulation of material in lysosomes as large inclusions. One severe type of the disease is Icell disease (inclusion –cell disease, GlcNAcPhosphotransferase gene mutant). TaySachs disease results from a deficiency of the enzyme (Nhexosaminidase A) whose function is to degrade gangliosides, a major ponent of brain cell membranes. 表 1. 神经鞘脂 贮 积病 疾病 缺失酶类 主要贮积底物 后果 GM1神经节苷脂贮积症 GM1半乳糖苷酶 神 经 节 苷 脂GM1 智力迟钝 ， 肝脏肥大 ， 骨骼受累 ， 2岁前死亡 泰－萨二氏病 己糖胺酶 A 神 经 节 苷 脂GM2 智力迟钝 ， 失明 ， 3岁前死亡 法布莱氏病 半乳糖苷酶 A 三己糖神经酰胺 皮疹 ， 肾功能丧失 ， 下肢疼痛 山霍夫氏病 己糖胺酶 A和 B 神 经 节 苷 脂GM2和红细胞糖苷酯 与泰－萨氏疾病症状相似 ，但发展更快 高歇氏病 葡糖脑苷酯酶 葡糖脑苷脂 肝脏和脾脏肿大 ， 长骨腐蚀 ， 只在婴儿期发生智力迟钝 尼 皮二氏病 鞘磷脂水解酶 鞘磷脂 肝脏和脾脏肿大 ， 智力迟钝 Farber’s 脂肪肉芽肿病 神经酰胺水解酶 神经酰胺 疼痛性与退行性的关节变形 ， 皮肤瘤 ， 几年内死亡 Krabbe’s 病 半乳糖脑苷酯酶 半乳糖脑苷脂 髓磷脂缺失 ， 智力迟钝 ， 2岁前死亡 脑硫脂沉积 芳基硫酸酯酶 脑硫脂 智力迟钝 ， 前十年死亡 D. Biogenesis of Lysosomes Figure 623 The transport of newly synthesized lysosomal hydrolases to lysosomes. The precursors of lysosomal hydrolases are covalently modified by the addition of mannose 6phosphate in the CGN. They then bee segregated from all other types of proteins in the TGN because a specific class of transport vesicles budding from the TGN concentrates mannose 6phosphatespecific receptors, which bind the modified lysosomal hydrolases. These vesicles subsequently fuse with late endosomes. At the low pH of the late endosome the hydrolases dissociate from the receptors, which are recycled to the Golgi apparatus for further rounds of transport. In late endosomes the phosphate is removed from the mannose on the hydrolases, further ensuring that the hydrolases do not return to the Golgi apparatus with the receptor. Mannose 6phosphate residues target proteins to lysosomes Targeting of soluble lysosomal enzymes to endosomes and lysosomes by M6P tag Phosphorylation of mannose residues on lysosomal enzymes catalyzed by two enzymes Recognition site binds to Signal patch GlcNAc phosphotransferase phosphodiesterase Figure 640. The mannose 6phosphate (M6P) pathway, the major route for targeting lysosomal enzymes to lysosomes. Precursors of lysosomal enzymes migrate from the rER to the cisGolgi where mannose residues are phosphorylated. In the TGN, the phosphorylated enzymes bind to M6P receptors, which direct the enzymes into vesicles coated with the clathrin. The clathrin lattice surrounding these vesicles is rapidly depolymerized to its subunits, and the uncoated transport vesicles fuse with late endosomes. Within this lowpH partment, the phosphoryl。