Architecture and dynamics of a desmosome-endoplasmic reticulum complex

Area of Science:

• Cell Biology
• Cytoskeleton Dynamics
• Subcellular Architecture

Background:

• The endoplasmic reticulum (ER) is a dynamic organelle involved in crucial cellular processes like stress response, calcium signaling, and lipid transfer.
• The ER network interacts with various cellular membranes, but its precise relationship with the cytoskeleton and cell junctions is not fully understood.

Purpose of the Study:

• To investigate the previously unknown association between the endoplasmic reticulum (ER) and keratin intermediate filaments and desmosomal cell-cell junctions.
• To elucidate the structural and functional implications of this novel ER interaction.

Main Methods:

• High-resolution volume electron microscopy was employed to visualize the subcellular architecture.
• Perturbation experiments were conducted on desmosomes and keratin filaments to assess their impact on ER organization.

Main Results:

• A previously unrecognized association between the ER and desmosomes/keratin filaments was discovered.
• Peripheral ER forms distinct arrangements at desmosomes, maintaining nanometer proximity to keratin filaments and the desmosome plaque.
• Disruption of desmosomes or keratin filaments altered ER organization, mobility, and the expression of ER stress-related genes.

Conclusions:

• Desmosomes and the keratin cytoskeleton play a regulatory role in the distribution, function, and dynamics of the ER network.
• This study uncovers a novel subcellular architecture integrating ER tubules with epithelial intercellular junctions.