Experimental Physics I, University of Bayreuth, Bayreuth, Germany.
Experimental Physics I, University of Bayreuth, Bayreuth, Germany.
Biophys J. 2021 Jun 15;120(12):2532-2542. doi: 10.1016/j.bpj.2021.04.023. Epub 2021 Apr 29.
The endoplasmic reticulum (ER) is a vital organelle in mammalian cells with a complex morphology. Consisting of sheet-like cisternae in the cell center, the peripheral ER forms a vast tubular network on which a dispersed pattern of a few hundred specialized domains (ER exit sites (ERESs)) is maintained. Molecular details of cargo sorting and vesicle formation at individual ERESs, fueling the early secretory pathway, have been studied in some detail. The emergence of spatially extended ERES patterns, however, has remained poorly understood. Here, we show that these patterns are determined by the underlying ER morphology, suggesting ERESs to emerge from a demixing process that is quenched by the ER network topology. In particular, we observed fewer but larger ERESs when transforming the ER network to more sheet-like morphologies. In contrast, little to no changes with respect to native ERES patterns were observed when fragmenting the ER, indicating that hampering the diffusion-mediated coarse graining of domains is key for native ERES patterns. Model simulations support the notion of effective diffusion barriers impeding the coarse graining and maturation of ERES patterns. We speculate that tuning a simple demixing mechanism by the ER topology allows for a robust but flexible adaption of ERES patterns, ensuring a properly working early secretory pathway in a variety of conditions.
内质网（ER）是哺乳动物细胞中一种具有复杂形态的重要细胞器。内质网的中心由片状的潴泡组成，外周 ER 形成一个巨大的管状网络，其上维持着几百个分散的特殊结构域（内质网出口位点（ERES））。在个别 ERES 处进行货物分拣和囊泡形成的分子细节已经进行了一些详细的研究，为早期分泌途径提供燃料。然而，空间扩展的 ERES 模式的出现仍然知之甚少。在这里，我们表明这些模式是由基础 ER 形态决定的，这表明 ERES 是从一个分相过程中出现的，该过程被 ER 网络拓扑结构所猝灭。具体来说，当将 ER 网络转化为更片状的形态时，我们观察到的 ERES 更少但更大。相比之下，当 ER 碎片化时，与原生 ERES 模式几乎没有变化，这表明阻碍扩散介导的结构域粗粒化对于原生 ERES 模式是关键的。模型模拟支持了有效扩散障碍阻碍 ERES 模式粗粒化和成熟的概念。我们推测，通过 ER 拓扑调整简单的分相机制，可以实现 ERES 模式的稳健但灵活的适应，确保在各种条件下早期分泌途径的正常运作。
