Departments of Dermatology and Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA, USA.
Advanced Imaging Center, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Nat Cell Biol. 2023 Jun;25(6):823-835. doi: 10.1038/s41556-023-01154-4. Epub 2023 Jun 8.
The endoplasmic reticulum (ER) forms a dynamic network that contacts other cellular membranes to regulate stress responses, calcium signalling and lipid transfer. Here, using high-resolution volume electron microscopy, we find that the ER forms a previously unknown association with keratin intermediate filaments and desmosomal cell-cell junctions. Peripheral ER assembles into mirror image-like arrangements at desmosomes and exhibits nanometre proximity to keratin filaments and the desmosome cytoplasmic plaque. ER tubules exhibit stable associations with desmosomes, and perturbation of desmosomes or keratin filaments alters ER organization, mobility and expression of ER stress transcripts. These findings indicate that desmosomes and the keratin cytoskeleton regulate the distribution, function and dynamics of the ER network. Overall, this study reveals a previously unknown subcellular architecture defined by the structural integration of ER tubules with an epithelial intercellular junction.
内质网（ER）形成一个动态网络，与其他细胞膜接触，以调节应激反应、钙信号和脂质转移。在这里，我们使用高分辨率体积电子显微镜发现，内质网与角蛋白中间丝和桥粒细胞-细胞连接形成了一个以前未知的关联。外周内质网在桥粒处组装成镜像排列，并与角蛋白丝和桥粒细胞质斑块保持纳米级接近。内质网管与桥粒稳定结合，桥粒或角蛋白丝的扰动改变内质网的组织、流动性和内质网应激转录本的表达。这些发现表明桥粒和角蛋白细胞骨架调节内质网网络的分布、功能和动力学。总的来说，这项研究揭示了一个以前未知的亚细胞结构，由内质网管与上皮细胞间连接的结构整合定义。
