第 2 讲细胞的跨膜转运
载体蛋白介导的易化扩散
葡萄糖转运蛋白 GLUT Glucose transporter (GLUT)
葡萄糖转运蛋白 GLUT 转运机制示意图
Overall structure of the human glucose transporter GLUT1 D Deng et al. Nature 510, 121-125 (2014) doi:10.1038/nature13306
简单扩散和易化扩散动力学的比较
离子通道介导的扩散 钠 钾离子通道离子通道的门控机制
离子通道介导的扩散 钾离子通道 离子通道的门控机制
膜片钳技术检测单个电压依赖性钠离子通道的开关状态
电压门控机制 电压门控的 L- 型钙离子离子通道 Voltage-dependent L-Type Calcium Channels
电压门控的 Cl - 离子通道 Voltage-dependent Ionic Channels 电压门控机制
电压门控机制 电压感应元件 voltage sensor
钠泵 Na + -K + -ATPase
钠泵 (Na + -K + -ATPase) 酶促工作周期
钠泵 Na + -K + -ATPase 的跨膜拓扑结构
钠泵 Na + -K + -ATPase 的三维晶体结构
Structure and domain organization of P-type ATPases
Structure and domain organization of P-type ATPases Morth JP, Pedersen BP, Buch-Pedersen MJ, Andersen JP, Vilsen B, Palmgren MG, Nissen P, 2011
P2 型离子泵 名称 比例 定位 亚基组成 / 分类 钠泵 1ATP/3Na/2K 上皮细胞基底面质膜 αβ / P2C 质子泵 1ATP/2H/2K (ph 6.1) 胃壁细胞 αβ / P2C 1ATP/1H/1K (ph<3.0) 肾小管细胞 小肠粘膜细胞顶端 质膜钙泵 1ATP/1H/1Ca 细胞质膜 α / P2B 肌浆网钙泵 1ATP/2H/2Ca 肌浆网膜 α / P2A
囊泡质子泵 V-type H + Pump 细胞胞内囊泡如溶酶体 lysosomes, 胞吞小体 endosomes, 分泌囊泡 secretory vesicles, 储存囊泡 storage vesicles Golgi 器 Golgi apparatus, 其包被膜都含有一种囊泡型质子泵 (vacuolar-type or V-type) H + -ATPase, 将质子从胞浆泵到囊泡之中 囊泡中的低 ph 值对于蛋白分拣 受体与配体的分离 酸性水解酶 (acid hydrolases) 的最佳活性, 神经递质在囊泡中的积累, 都非常重要 与胃的质子泵不同,V- 型质子泵的转运不依赖于 K + 的转运
利用离子梯度的跨膜转运蛋白 -Na + - 葡萄糖共转运蛋白 (SGLT)
毛刷边缘膜所形成的囊泡保持其钠离子梯度驱动的葡萄糖转运功能 Na + -driven glucose uptake into brush border membrane vesicles
在体情况下上皮细胞毛刷边缘膜在钠离子梯度的驱动下转运葡萄糖进入细胞 Na + -driven glucose uptake into epithelial cells
利用钠离子梯度的跨膜交换蛋白 Na + -Ca 2+ 交换蛋白 ;Na + -H + 交换蛋白 3
利用钠离子梯度的跨膜转运蛋白 Na + -Ca 2+ 交换蛋白的离子转运机制 Fig. 5 Cartoon representation of Na+/Ca2+ exchange of NCX in the classical 3Na+:1Ca2+ extrusion mode. Liao J, Li H, Zeng WZ, Sauer DB, Belmares R, and Jiang YX (2012)
代表性交换蛋白
Ion gradients, channels, and transporters in a typical cell
Family SLC1 (7) SLC2 (14) SLC3 (2) SLC4 (10) SLC5 (8) SLC6 (16) SLC7 (14) SLC8 (3) SLC9 (9) SLC10 (6) SLC11 (2) SLC12 (9) SLC13 (5) SLC14 (2) SLC15 (4) SLC 超家族溶质载体蛋白的一些亚家族 (I) Description Glutamate transporters Facilitated transport of hexoses Heavy subunits of heterodimeric amino acid transporters (with SLC7) HCO 3 - exchangers and cotransporters Na + /glucose cotransporters Na + - and Cl - -coupled cotransport of "neurotransmitters" Transporter subunits of heterodimeric amino acid transporters (with SLC3) Na-Ca exchangers Na-H exchangers Na/bile salt cotransporters H + -driven metal ion cotransporters Cation-coupled Cl - cotransporters Na + -coupled sulfate and carboxylate cotransporters Facilitated transport of urea H + -driven oligopeptide cotransporters Examples EAAT1 GLUT1, GLUT4 AE1 (Cl-HCO 3 exchanger); NBCe1 (electrogenic Na/HCO 3 cotransporter); NBCn1 (electroneutral Na/HCO 3 cotransporter); NDCBE (Na + -driven Cl-HCO 3 exchanger) SGLT1 to 5 (glucose) B 0 AT1 (Na + -coupled amino acid) GAT1-3, GBT1 (Na + - and Cl - -coupled GABA) ATB 0+ (Na + - and Cl - -coupled amino acids) NCX1 to 3 NHE1 to 8 DMT1 NKCC1, NKCC2 (Na/K/Cl cotransporter) NCC (Na/Cl cotransporter) KCC1 (K/Cl cotransporter) NaDC1 (mono-, di-, and tricarboxylates) NaSi (sulfate) UT PepT1
Family SLC16 (14) SLC17 (8) SLC18 (3) SLC19 (3) SLC20 (2) SLC21 (11) SLC22 (18) SLC23 (4) SLC26 (10) SLC 超家族溶质载体蛋白的一些亚家族 (II) Description Monocarboxylate transporters Type I Na/phosphate cotransporters and vesicular Glu transporters Vesicular amine transporters Folate/thiamine transporters Type III Na/phosphate cotransporters Organic anion transporters Organic cations, anions, zwitterions Na/ascorbic acid transporters Multifunctional anion exchangers Examples MCT1 (H + -coupled monocarboxylate cotransporter) TAT1 (facilitated diffusion of aromatic amino acids) NaPi-I NaPi-III OATP PGT OCT1 to 3 (facilitated diffusion or organic cations); OAT1 to 5 (exchange or facilitated diffusion of organic anions); URAT (urate exchanger) DRA (Cl-HCO 3 exchanger); Pendrin (exchanges HCO 3 -, Cl -, or I - ); CFEX (exchanges Cl -, HCO 3 -, oxalate, formate) SLC28 (3) SLC34 (3) SLC36 (4) SLC38 (6) SLC39 (14) SLC40 (1) SLC42 (3) Na/nucleoside transporters Type II Na/phosphate cotransporters H + -coupled amino acid cotransporters Na + -driven neutral amino acids (system A and N) Metal ion transporters Basolateral Fe transporter* NH 3 channels NaPi-IIa, NaPi-IIc PAT1 SNAT3 (cotransports amino acids with Na + in exchange for H + ) System N (cotransports amino acids with Na + in exchange for H + ) SNAT1, 2, 4 (system A cotransports amino acids with Na + ) ZIP1 (uptake of Zn 2+ ) Ferroportin (MTP1, Fe 2+ ) RhAG
穿胞转运 Transcytosis 内吞 内吞小泡转运途径 endocytosis 路径 1 示胞外物质从细胞一侧转移至另一侧 穿胞转运 transcytosis 路径 2 显示与内吞小体融合, 然后可通过 3 重新加入膜结构 ; 胞吐 路径 4 示小泡能被胞内溶酶体所消化
Figure 2-11 Mechanism of pinocytosis
Figure 2-13 Formation of proteins, lipids, and cellular vesicles by the endoplasmic reticulum and Golgi apparatus.
突触小泡的胞吐与神经递质的释放 SNARE complex v-snare: Synaptobrevin t-snare: SNAP-25 Syntaxin Figure 8-16 Model of synaptic vesicle fusion and exocytosis. NSF, N-ethylmaleimide-sensitive factor; SNAP-25, synaptosome-associated protein 25 kda; α-snap, soluble NSF attachment protein; SNARE, SNAP receptor.
第 2 讲作业 1 细胞质膜双脂层脂肪屏障 The Lipid Barrier of the Plasma Membrane - 胞内液 胞外液主要成份差别 2 载体蛋白介导的易化扩散 Carrier-mediated Facilitated Diffusion GLUT1, GLUT4 3 离子通道 ionic channels - 离子选择性表征 selectivity filter, 单个离子通道大小的表征 - 电导 ps 4 钾离子通道的离子选择性是由什么氨基酸残基构成? 5 P2 型离子泵 P2 ATPases - P2C (SERCA), P2B (PMCA), P2A (NKA, H + -ATPase) 6 共转运蛋白 Co-transporters - SGLT 7 交换蛋白 Exchangers NCX, NHX 8 主要溶质载体蛋白家族 Major SLC class - SLC2, SLC5, SLC8, SLC38 9 内吞与胞吐 Endocytosis / Exocytosis (clathrin coated pits / SNARE complex)