Journal Article

Architecture and dynamics of a desmosome–endoplasmic reticulum complex

Kowalczyk, Andrew P., Petruncio, Alyson, Saalfeld, Stephan, Weigel, Aubrey V., Ackerman, David, Preibisch, Stephan, Park, Woohyun, Aaron, Jesse S., Chew, Teng-Leong, Hoffman, Coryn L., Giang, William, Bogovic, John, Wayne Vogl, A., Stahley, Sara N., Bharathan, Navaneetha Krishnan, Trautman, Eric T., Heinrich, Larissa, Bennett, Davis, Khuon, Satya

2023

Overview

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. Bharathan et al. discover that the endoplasmic reticulum associates with keratin intermediate filaments and desmosomal cell–cell junctions, and that desmosomes and the keratin cytoskeleton regulate the distribution, dynamics and function of the endoplasmic reticulum network.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 14/19 / 14/28 / 14/35 / 631/80/128/1580 / 631/80/642/1463 / 631/80/79/1416 / Biomedical and Life Sciences / Calcium signalling / Cancer Research / Cell Biology / Cell junctions / Cell membranes / Cellular communication / Cellular stress response / Contact stresses / Cytoskeleton / Cytoskeleton - metabolism / Desmosomes / Desmosomes - chemistry / Desmosomes - metabolism / Desmosomes - ultrastructure / Developmental Biology / Electron microscopy / Endoplasmic reticulum / Endoplasmic Reticulum - metabolism / Filaments / Intermediate filaments / Intermediate Filaments - metabolism / Intermediate Filaments - ultrastructure / Keratin / Keratins - metabolism / Life Sciences / Lipids / Perturbation / Stem Cells / Tubules