Group of Applied Mathematics and Computational Biology, Ecole Normale Superieure, IBENS, Paris, France.
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Nat Cell Biol. 2018 Oct;20(10):1118-1125. doi: 10.1038/s41556-018-0192-2. Epub 2018 Sep 17.
The endoplasmic reticulum (ER), a network of membranous sheets and pipes, supports functions encompassing biogenesis of secretory proteins and delivery of functional solutes throughout the cell. Molecular mobility through the ER network enables these functionalities, but diffusion alone is not sufficient to explain luminal transport across supramicrometre distances. Understanding the ER structure-function relationship is critical in light of mutations in ER morphology-regulating proteins that give rise to neurodegenerative disorders. Here, super-resolution microscopy and analysis of single particle trajectories of ER luminal proteins revealed that the topological organization of the ER correlates with distinct trafficking modes of its luminal content: with a dominant diffusive component in tubular junctions and a fast flow component in tubules. Particle trajectory orientations resolved over time revealed an alternating current of the ER contents, while fast ER super-resolution identified energy-dependent tubule contraction events at specific points as a plausible mechanism for generating active ER luminal flow. The discovery of active flow in the ER has implications for timely ER content distribution throughout the cell, particularly important for cells with extensive ER-containing projections such as neurons.
内质网（ER）是一个由膜片和管道组成的网络，支持包括分泌蛋白的生物发生和功能性溶质在整个细胞内传递的功能。分子在 ER 网络中的流动性使这些功能成为可能，但仅通过扩散不足以解释穿过超微结构距离的腔运输。鉴于调节 ER 形态的蛋白质发生突变会导致神经退行性疾病，因此了解 ER 的结构-功能关系至关重要。在这里，超分辨率显微镜和对 ER 腔蛋白的单个颗粒轨迹的分析表明，ER 的拓扑结构与其腔内容物的不同运输模式相关：在管状连接处有一个主要的扩散成分，而在管状中则有一个快速流动的成分。随着时间的推移解析的颗粒轨迹方向显示出 ER 内容的交流电，而快速 ER 超分辨率则在特定点识别出能量依赖性的管状收缩事件，这是产生活跃 ER 腔流的合理机制。ER 中活性流的发现对 ER 内容在整个细胞中的及时分布具有重要意义，特别是对于含有广泛 ER 突起的细胞（如神经元）而言尤为重要。
