Overview

Vesicle transport refers to transport the substance to the destination and fuse融合 with the target organelle or plasma membrane by vesicles budding出芽 from the surface of an organelle or endocytic vesicles内吞囊泡 formed from the plasma membrane.

membrane flow胞内膜流动
highly organized, directional and maintains dynamic equilibrium

Endocytosis (胞吞作用) and Exocytosis (胞吐作用)

Endocytosis (胞吞作用): The formation of vesicles by invagination内陷 of the plasma membrane, wrapping substances outside the cell or on the plasma membrane into the vesicles and transporting them into the cells

Exocytosis (胞吐作用): The process by which secretory vesicles carrying intracellular contents fuse with the plasma membrane and release the contents outside the cell.

Endocytosis

the vesicles formed by invagination of the plasma membrane are called endocytic vesicles胞吞泡

有两种胞吞👇
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phagocytosis吞噬作用

＞250nm

Endocytic vesicles formed by phagocytosis is called phagosome吞噬体

occurs in macrophages 巨噬细胞 and neutrophils 中性粒细胞

remove pathogens病原体 and senescent衰老 or apoptotic凋亡 cells

需要被吞噬物 bind to the receptors on membrane

pseudopod伪足

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pinocytosis胞吞作用

＜250nm

occurs in all kind of cells

有4种

  1. Clathrin dependent endocytosis (网格蛋白依赖的胞吞作用)
  2. Caveola dependent endocytosis (胞膜窖依赖的胞吞作用)
  3. Macropinocytosis(大型胞饮作用)
  4. Clathrin and caveola independent endocytosis (非网格蛋白/胞膜窖依赖的胞吞作用)

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Exocytosis

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Constitutive exocytosis pathway (组成型胞吐途径)

从TGN分泌与细胞膜结合,可以变成细胞膜上的脂质与蛋白,也可以形成ECM

Regulatory exocytosis pathway (调节型胞吐途径)

specialized secretory cells

分泌物比如激素,消化酶等,先形成secretory vesicles呆在细胞膜旁边
等胞外信号刺激后再与细胞膜融合释放分泌物

Coated Vesicles

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distinguished by their coat proteins,有3种

  1. Clathrin/AP-coated
    网格蛋白/接头蛋白
    TGN → PM,lysosome
    The receptor-mediated endocytosis pathway
  2. COPI-coated
    CGN → ER
  3. COPII-coated
    ER → CGN

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Clathrin/AP coated Vesicles

structure

double-coated vesicles

外面的一层是clathrin protein网格蛋白,里面一层是 adaptin complex接头复合物

clathrin subunit consist of 3 dimers(1 heavy chain,1 light chain),form a triskelion三腿结构
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formation

  1. Coat assembly and cargo selection (包被组装和被转运蛋白的选择) ——Clathrin，Adaptin，ARF
  2. Coated Pit formation and budding (包被小泡形成和的出芽)
  3. Vesicle formation (膜泡形成) —— Dynamin
  4. Uncoating (膜泡脱包被) ——ARF(ARF-GTP to ARF-GDP)，HSP70(ATP to ADP)

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上面4条明显不说人话,下面是中文解释

  1. 细胞膜上的受体结合了要运送的货物后,会召集adaptin接头蛋白,同时再ARF的帮助下,招募chathrin
  2. 招募过程中形成了鼓出来的细胞膜
  3. dynamin发动蛋白消耗GTP构象变化,夹断形成膜泡
  4. ARF结合的GTP变成GDP,ARF失活,adaptin和chathrin脱落

Receptor-Mediated Endocytosis RME

Cells use RME to import selected extracellular macromolecules.
比如胆固醇,胰岛素,Fe,维生素B12
流感与HIV也用RME感染细胞

LDL

Most cholesterol胆固醇 is transported in the blood as low-density lipoproteins LDLs

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LDL结合细胞膜上的受体后通过clathrin/ap-coated vesicle 进入细胞内
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endosome胞内体,是一个转运内吞的物质的细胞器,可以将受体与要转运的物质分离,然后把物质送到溶酶体降解

最终LDL受体返回细胞膜,LDL进入溶酶体被降解成游离的胆固醇

COP I Coated Vesicles

COP I mediate retrograde transport (逆向运输)
CGN → ER

recycle ER resident soluble and membrane proteins, which is an important pathway to recycle escaped proteins
是内质网回收错误分选的逃逸蛋白的重要途径

The recovery of escaped ER proteins is accomplished by receptors binding to retrieval signal回收信号

在内质网中驻留的可溶性蛋白(比如说分子伴侣)上面有retrieval signal可以与CGN上的受体结合形成COP I 被送回内质网

COP II Coated Vesicles

COP II mediate anterograde transport (顺向运输)
rER → CGN

The selectivity of cargo protein
COPII coat protein has receptor specifically binding to the sorting sequence on membrane or receptor protein to be transported
COPII外被蛋白具有特异性结合膜上或待运输受体蛋白上的分选序列的受体

Docking and Fusion of Vesicles to Target membrane

  1. Rab proteins and Rab effectors dock the vesicle to specific spots on the correct target membrane.
  2. SNARE proteins and SNARE regulators mediate the fusion of the vesicle membrane to the target membrane.

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Rab介导锚定,SNARE介导融合