最新考研资料：北京大学细胞生物学第六章基质与内膜(中)
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智力迟钝，失明，3岁前死 亡
皮疹，肾功能丧失，下肢 疼痛
与泰－萨氏疾病症状相似， 但发展更快
肝脏和脾脏肿大，长骨腐 蚀，只在婴儿期发生智力 迟钝 肝脏和脾脏肿大，智力迟 钝
疼痛性与退行性的关节变 形，皮肤瘤，几年内死亡
髓磷脂缺失，智力迟钝，2 岁前死亡
智力迟钝，前十年死亡
D. Biogenesis of Lysosomes
考研资料：北京大学细 胞生物学第六章基质与
内膜(中)
4. The structure and functions of Lysosomes
A. Characteristics of Lysosomes
① Lysosome is a heterogenous organelle:
Primary lysosomes Second lysosomes
Mannose 6-phosphate residues target proteins to lysosomes
Targeting of soluble lysosomal enzymes to endosomes and lysosomes by M-6-P tag
Phosphorylation of mannose residues on lysosomal enzymes catalyzed by two enzymes
Figure 6-23 The transport of newly synthesized lysosomal hydrolases to lysosomes. The
precursors of lysosomal hydrolases are covalently modified by the addition of mannose 6-phosphate in the CGN. They then become segregated from all other types of proteins in the TGN because a specific class of transport vesicles budding from the TGN concentrates mannose 6-phosphate-specific 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.
lysosomal enzymes to lysosomes. Precursors of lysosomal enzymes migrate from the rER to the cis-Golgi 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 low-pH compartment, the phosphorylated enzymes dissociate from the M6P receptors and then are dephosphorylated. The receptors recycle back to the Golgi, and the enzymes are incorporated into a different transport vesicle that buds from the late endosome and soon fuses with a lysosome. The sorting of lysosomal enzymes from secretory proteins thus occurs in the TGN, and these two classes of proteins are incorporated into different vesicles, which take different routes after they bud from the Golgi.[G. Griffiths et al., Cell 52:329; S. Kornfeld, Annu. Rev. Biochem. 61:307; and G. Griffiths and J. Gruenberg, Trends Cell Biol. 1:5]
GlcNAc phosphotransferase
Recognition site binds to Signal patch
phosphodiesterase
Figure 6-40. The mannose 6-phosphate (M6P) pathway, the major route for targeting
heterophagic autophagic Residual body
Primary Lys.
Second Lys
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Leabharlann Baidu贮 积症 泰－萨二氏病 法布莱氏病 山霍夫氏病
高歇氏病
尼-皮二氏病 Farber’s 脂肪肉芽肿 病 Krabbe’s 病
脑硫脂沉积
GM1-半乳糖苷 酶 己糖胺酶A -半乳糖苷酶A 己糖胺酶A和B
葡糖脑苷酯酶
鞘磷脂水解酶 神经酰胺水解酶
半乳糖脑苷酯酶
芳基硫酸酯酶
神经节苷脂 GM1
神经节苷脂 GM2 三己糖神经酰 胺 神经节苷脂 GM2 和 红 细 胞 糖苷酯 葡糖脑苷脂
鞘磷脂
神经酰胺
半乳糖脑苷脂
脑硫脂
智力迟钝，肝脏肥大，骨 骼受累，2岁前死亡
皮疹，肾功能丧失，下肢 疼痛
与泰－萨氏疾病症状相似， 但发展更快
肝脏和脾脏肿大，长骨腐 蚀，只在婴儿期发生智力 迟钝 肝脏和脾脏肿大，智力迟 钝
疼痛性与退行性的关节变 形，皮肤瘤，几年内死亡
髓磷脂缺失，智力迟钝，2 岁前死亡
智力迟钝，前十年死亡
D. Biogenesis of Lysosomes
考研资料：北京大学细 胞生物学第六章基质与
内膜(中)
4. The structure and functions of Lysosomes
A. Characteristics of Lysosomes
① Lysosome is a heterogenous organelle:
Primary lysosomes Second lysosomes
Mannose 6-phosphate residues target proteins to lysosomes
Targeting of soluble lysosomal enzymes to endosomes and lysosomes by M-6-P tag
Phosphorylation of mannose residues on lysosomal enzymes catalyzed by two enzymes
Figure 6-23 The transport of newly synthesized lysosomal hydrolases to lysosomes. The
precursors of lysosomal hydrolases are covalently modified by the addition of mannose 6-phosphate in the CGN. They then become segregated from all other types of proteins in the TGN because a specific class of transport vesicles budding from the TGN concentrates mannose 6-phosphate-specific 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.
lysosomal enzymes to lysosomes. Precursors of lysosomal enzymes migrate from the rER to the cis-Golgi 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 low-pH compartment, the phosphorylated enzymes dissociate from the M6P receptors and then are dephosphorylated. The receptors recycle back to the Golgi, and the enzymes are incorporated into a different transport vesicle that buds from the late endosome and soon fuses with a lysosome. The sorting of lysosomal enzymes from secretory proteins thus occurs in the TGN, and these two classes of proteins are incorporated into different vesicles, which take different routes after they bud from the Golgi.[G. Griffiths et al., Cell 52:329; S. Kornfeld, Annu. Rev. Biochem. 61:307; and G. Griffiths and J. Gruenberg, Trends Cell Biol. 1:5]
GlcNAc phosphotransferase
Recognition site binds to Signal patch
phosphodiesterase
Figure 6-40. The mannose 6-phosphate (M6P) pathway, the major route for targeting
heterophagic autophagic Residual body
Primary Lys.
Second Lys
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Leabharlann Baidu贮 积症 泰－萨二氏病 法布莱氏病 山霍夫氏病
高歇氏病
尼-皮二氏病 Farber’s 脂肪肉芽肿 病 Krabbe’s 病
脑硫脂沉积
GM1-半乳糖苷 酶 己糖胺酶A -半乳糖苷酶A 己糖胺酶A和B
葡糖脑苷酯酶
鞘磷脂水解酶 神经酰胺水解酶
半乳糖脑苷酯酶
芳基硫酸酯酶
神经节苷脂 GM1
神经节苷脂 GM2 三己糖神经酰 胺 神经节苷脂 GM2 和 红 细 胞 糖苷酯 葡糖脑苷脂
鞘磷脂
神经酰胺
半乳糖脑苷脂
脑硫脂
智力迟钝，肝脏肥大，骨 骼受累，2岁前死亡