Architecture and dynamics of a desmosome–endoplasmic reticulum complex

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

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8 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)823-835
Number of pages13
JournalNature Cell Biology
Issue number6
StatePublished - Jun 2023

All Science Journal Classification (ASJC) codes

  • Cell Biology

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