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- W4366171930 abstract "Desmosomes are adhesive intercellular junctions that provide strength and integrity to the epidermis. However, little is known about how desmosomes are integrated with subcellular organelles essential for epidermal structure and differentiation. Using electron microscopy and live-cell fluorescence imaging, we found that peripheral ER tubules associate with desmosomal cell-cell contacts in a variety of cultured epithelia and tissues, including skin. Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) and 3D reconstructions at nanometer resolution revealed intricate associations of ER tubules with the desmosome plaque. Keratin filaments, which anchor to desmosomes, aligned and intertwined with ER tubules on either side of the desmosome. Manual and semi-automated segmentation of volume EM data revealed mirror image-like arrangements of ER and keratin at virtually all mature desmosomes. Live-cell imaging demonstrated that ER tubules, which are normally highly dynamic, were immobilized at junctional desmosomes, both during steady-state conditions and dynamic processes like desmosome fusion. Further, ER at cell-cell borders remained anchored to desmosomes following microtubule depolymerization, whereas ER at cell-free edges retracted toward the cell interior. Genetic disruption of desmosomes altered ER morphology and dynamics. Additionally, expression of a keratin 14 mutant that causes the epidermal blistering disease, epidermolysis bullosa simplex, shifted ER morphology from tubular to sheet-like. These data demonstrate that desmosomes and keratins are key regulators of ER organization and mobility. Our results reveal a previously unknown subcellular complex comprising the ER, desmosomes, and keratin filaments, and expose an unappreciated therapeutic target for desmosomal and keratin skin diseases." @default.
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- W4366171930 date "2023-05-01" @default.
- W4366171930 modified "2023-09-28" @default.
- W4366171930 title "772 Structure of a novel endoplasmic reticulum-desmosome complex" @default.
- W4366171930 doi "https://doi.org/10.1016/j.jid.2023.03.781" @default.
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