摘要
细胞内的囊泡运输大致分两类,一类是经典的马达蛋白与细胞骨架依赖性的长距离运输,另一类是局域的短距离运输.短距离运输也有明确的方向,却不依赖马达蛋白或细胞骨架,长期以来科研人员对短距离囊泡运输的原理缺乏清晰的理解.以突触囊泡(synaptic vesicle,SV)的定向转运为例,该研究发现了一种新的由相分离介导的、钙信号调控的、定向的运输方式.具体来讲,一个名为Pclo(Piccolo)的支架蛋白,通过与囊泡发生受钙信号调控的相分离,一方面介导囊泡从储备池的提取,另一方面促进囊泡在活性区的栓系.此外,该研究还发现,在普通的动物细胞中,TFG(Trk-fused gene)的相分离可以介导COPⅡ(coat protein complex Ⅱ)囊泡从内质网(endoplasmic reticulum,ER)到内质网-高尔基体中间体(ER-Golgi intermediate compartment,ERGIC)的转运.因此,相分离提供了一种普适的介导短距离囊泡定向运输的方式.
Abstract
Cellular vesicles are moved via two distinct routes:the canonical motor-powered transport,which moves along cytoskeletons typically over long distances,and local and short-distance transport.The short-distance transport is also with directions but does not involve molecular motors and cytoskeletons.The molecular mechanisms underlying short-distance vesicle transport are totally unknown.Using SV(synaptic vesicle)transport as a paradigm,this study discovers a new way of short-distance vesicle transport mediated by phase separation in a Ca2+-regulated and directional manner.Specifically,a scaffold called Pclo(Piccolo)in the presynaptic bouton un-dergoes phase separation with SV.On the one hand,Pclo can extract SVs from the reserve pool,on the other hand,Pclo can facilitate SV tethering on the active zone.In addition,this study further finds a protein called TFG(Trk-fused gene)can facilitate COPⅡ(coat protein complex Ⅱ)vesicles transport from ER(endoplasmic reticulum)to the ERGIC(ER-Golgi intermediate compartment)via phase separation.Therefore,phase separation may be a general mechanism for short-distance vesicle transport in cells.
基金项目
国家自然科学基金委基础科学中心项目(82188101)
国家重点研发计划(2019YFA0508402)
深圳市孔雀计划(KQTD20210811090115021)
NETL
NSTL
万方数据