囊泡运输的分子细胞机制

Molecular and Cellular Mechanism of Vesicle Trafficking

内膜系统构成了细胞及细胞器之间的天然屏障,保证重要的生命活动在相对独立的空间内进行。细胞内膜性细胞器之间的物质(如蛋白质、脂类)的运输主要是通过囊泡完成的。囊泡运输需要货物分子、运输复合体、动力蛋白和微管等的参与以及多种分子的调节,包括出芽、锚定和融合等过程。从上世纪60年代开始,人们认识到细胞分泌的蛋白需要先进入内质网,再到高尔基体,然后分泌到其作用部位。之后,信号肽假说被提出和证明。随后的研究完善了囊泡运输的过程,包括经内质网到高尔基体的蛋白质分泌运输过程中关键的调控基因及其作用环节、蛋白质复合物SNARE(可溶性N-乙基马来酰亚胺敏感的融合蛋白附着蛋白受体)在囊泡锚定和融合中的作用机制等。在囊泡运输中的具有代表性的神经细胞突触囊泡中,触发突触囊泡融合的钙感受器(synaptotagmin)能快速准确地将钙信号传递到突触囊泡,通过与SNARE复合体等作用,实现与细胞膜融合并释放神经递质,最终完成神经信息的传递。该文从囊泡运输的研究历史回顾、已有研究成果以及未来展望等三个方面对囊泡运输分子细胞机制进行了阐述。

Endomembrane system constitutes natural barriers between cells and organelles to ensure that important life activities are regulated in compartments.The transport of cargoes such as proteins and lipids between membrane-bound organelles in cells is mainly mediated by vesicles.Vesicle trafficking requires the involvement of cargoes,transport complexes,motor proteins and microtubules,as well as many regulators in the process of vesicle budding,docking and fusion.Since 1960 s,the secretory pathway had been characterized by several key steps,firstly synthesizing in the endoplasmic reticulum,then entering into the Golgi apparatus and transporting soluble and membrane proteins to their appropriate destination in the cell.Later on,the signal peptide hypothesis was proposed.Further investigations have gained insights into the details of vesicle trafficking,including the discovery of key regulatory genes and their roles in the protein transport pathway from ER to Golgi,the role of SNAREs(soluble N-ethyl-maleimide-sensitive factor attachment protein receptors)in vesicle docking and fusion.In the neuronal synaptic vesicles,a typical model in vesicle trafficking,a calcium-binding protein(synaptotagmin)triggers synaptic vesicle fusion.Synaptagmin transmits calcium signals to synaptic vesicles which fuse with plasma membrane to release neurotransmitters through its interaction with SNARE complexes.Here we reviewed the molecular and cellular mechanism of vesicle trafficking by mainly focusing on three aspects,the history of studying vesicular trafficking,the current progress of this field and the future prospects.