Badu-Nkansah, K. | bioRxiv Science

bioRxiv2025

Compartmentalization of mRNA and Translation by Desmosomes

Subcellular compartmentalization enables cells to concentrate and locally regulate functions. Here we find that translational machinery is compartmentalized to the cell cortex in epidermal cells. Furthermore, we observed broad enrichment of transcripts at the cortex, establishing a novel axis of mRNA organization in these cells. Mechanistically, we identified the desmosomal protein, desmoplakin, to be essential for cortical recruitment of both ribosomes and mRNAs, through distinct mechanisms. While mRNA localization is usually proposed to promote local translation, we found that most cortical transcripts were translationally repressed. These findings reveal spatial and transcript-dependent features of the cortical translatome. One mediator of this regulation is the RNA-induced Silencing Complex (RISC) which is also cortically enriched in a desmoplakin-dependent manner. Under homeostatic conditions, cortical RISC associates with transcripts for cell adhesion and the cytoskeleton. Upon wounding RISC is delocalized from the cortex and its associated transcripts become translationally upregulated. Together our data demonstrate a desmosome-dependent cortical compartmentalization of translation that dynamically responds to barrier perturbations, including wounding.

cell biology↗

bioRxiv2019

Proteomic analysis of the desmosome identifies novel components required for skin integrity

Desmosomes are cell-cell adhesions necessary for the maintenance of tissue integrity in the skin and the heart. While the core components of the desmosome have been identified, peripheral components that modulate canonical desmosome functions or that have noncanonical roles remain largely unexplored. Here we used targeted proximity labeling approaches to elaborate the desmosome proteome in epidermal keratinocytes. Quantitative mass spectrometry analysis identified all core desmosome proteins while uncovering a diverse network of new constituents with broad molecular functions. By individually targeting the inner and outer dense plaques, we additionally define proteins enriched in these subcompartments. We validated a number of these novel desmosome-associated proteins and find that many show a dependence upon the core desmosomal protein, desmoplakin, for their localization. We further explored the mechanism of localization and function of two novel desmosome-associated adaptor proteins that we identified, Crk and Crkl. These proteins interacted with Dsg1 and require both Dsg1 and desmoplakin for robust cortical localization. Epidermal deletion of both Crk and CrkL in mice resulted in perinatal lethality with defects in desmosome morphology and keratin organization, thus demonstrating the utility of this dataset in identifying novel proteins required for desmosome-dependent epidermal integrity.

cell biology↗