Endoplasmic reticulum network heterogeneity guides diffusive transport and kinetics
Endoplasmic reticulum network heterogeneity guides diffusive transport and kinetics
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DOI：
10.1016/j.bpj.2023.06.022
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发表时间：
2023-08-08
影响因子：
3.4
通讯作者：
Koslover，Elena F.
中科院分区：
文献类型：
--
作者：
Scott，Zubenelgenubi C.;Koning，Katherine;Koslover，Elena F.
内质网（ER）是一个相互连接的片层和小管的动态网络，协调脂质，离子和蛋白质在整个细胞中的分布。其复杂的，动态的形态对其作为细胞内运输枢纽的功能的影响仍然知之甚少。为了阐明ER网络结构和动力学的功能后果，我们量化了COS7细胞中外周ER的异质性如何影响扩散性蛋白质转运。光活化的ER膜蛋白的体内成像表明它们以与在提取的网络结构上扩散颗粒的模拟一致的方式不均匀地扩散到相邻区域。使用一个最小的网络模型来表示微管重排，我们证明了ER网络动力学足够慢，扩散蛋白质运输的影响很小。此外，随机模拟揭示了ER网络异质性的一个新的后果：“热点”的存在，稀疏的扩散反应物更有可能找到对方。ER出口网站，专门的域调节货物出口从ER，被证明是不成比例地位于高度可访问的区域，进一步从细胞的外边界。结合体内实验与分析计算，定量图像分析和计算建模，我们演示了如何结构引导扩散蛋白质运输和反应的ER。
The endoplasmic reticulum (ER) is a dynamic network of interconnected sheets and tubules that orchestrates the distribution of lipids, ions, and proteins throughout the cell. The impact of its complex, dynamic morphology on its function as an intracellular transport hub remains poorly understood. To elucidate the functional consequences of ER network structure and dynamics, we quantify how the heterogeneity of the peripheral ER in COS7 cells affects diffusive protein transport. In vivo imaging of photoactivated ER membrane proteins demonstrates their nonuniform spreading to adjacent regions, in a manner consistent with simulations of diffusing particles on extracted network structures. Using a minimal network model to represent tubule rearrangements, we demonstrate that ER network dynamics are sufficiently slow to have little effect on diffusive protein transport. Furthermore, stochastic simulations reveal a novel consequence of ER network heterogeneity: the existence of "hot spots" where sparse diffusive reactants are more likely to find one another. ER exit sites, specialized domains regulating cargo export from the ER, are shown to be disproportionately located in highly accessible regions, further from the outer boundary of the cell. Combining in vivo experiments with analytic calculations, quantitative image analysis, and computational modeling, we demonstrate how structure guides diffusive protein transport and reactions in the ER.