Kalaidzidis Inna, Miaczynska Marta, Brewińska-Olchowik Marta, Hupalowska Anna, Ferguson Charles, Parton Robert G, Kalaidzidis Yannis, Zerial Marino
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
J Cell Biol. 2015 Oct 12;211(1):123-44. doi: 10.1083/jcb.201311117.
Endocytosis allows cargo to enter a series of specialized endosomal compartments, beginning with early endosomes harboring Rab5 and its effector EEA1. There are, however, additional structures labeled by the Rab5 effector APPL1 whose role in endocytic transport remains unclear. It has been proposed that APPL1 vesicles are transport intermediates that convert into EEA1 endosomes. Here, we tested this model by analyzing the ultrastructural morphology, kinetics of cargo transport, and stability of the APPL1 compartment over time. We found that APPL1 resides on a tubulo-vesicular compartment that is capable of sorting cargo for recycling or degradation and that displays long lifetimes, all features typical of early endosomes. Fitting mathematical models to experimental data rules out maturation of APPL1 vesicles into EEA1 endosomes as a primary mechanism for cargo transport. Our data suggest instead that APPL1 endosomes represent a distinct population of Rab5-positive sorting endosomes, thus providing important insights into the compartmental organization of the early endocytic pathway.
内吞作用使货物能够进入一系列特殊的内体区室,起始于含有Rab5及其效应器EEA1的早期内体。然而,还有一些由Rab5效应器APPL1标记的其他结构,其在内吞运输中的作用尚不清楚。有人提出,APPL1囊泡是转化为EEA1内体的运输中间体。在这里,我们通过分析超微结构形态、货物运输动力学以及APPL1区室随时间的稳定性来测试该模型。我们发现APPL1存在于一个管状囊泡区室中,该区域能够对货物进行分类以便回收或降解,并且具有较长的寿命,所有这些都是早期内体的典型特征。将数学模型与实验数据拟合排除了APPL1囊泡成熟为EEA1内体作为货物运输的主要机制。相反,我们的数据表明APPL1内体代表了Rab5阳性分拣内体的一个独特群体,从而为早期内吞途径的区室组织提供了重要见解。