Biology subjects

Hlavaty, D.

Publications and source records attributed to Hlavaty, D..

2 recordsLinked to original sources

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↗

bioRxiv2020

Ndel1 promotes keratin assembly and desmosome stability

Keratin intermediate filaments form dynamic polymer networks that organize in specific ways dependent on the cell type, the stage of the cell cycle, and the state of the cell. In differentiated cells of the epidermis, they are organized by desmosomes, cell-cell adhesion complexes which provide essential mechanical integrity to this tissue. Despite this, we know little about how keratin organization is controlled and whether desmosomes actively promote keratin assembly in addition to binding pre-assembled filaments. We recently discovered that Ndel1 is a desmosome-associated protein in differentiated epidermis. Here, we show that Ndel1 binds directly to keratin subunits through a motif conserved in all intermediate filament proteins. Further, Ndel1 is necessary for robust desmosome-keratin association and sufficient to reorganize keratins to distinct cellular sites. Lis1, a Ndel1 binding protein, is required for desmosomal localization of Ndel1, but not for its effects on keratin filaments. Finally, we use mouse genetics to demonstrate that loss of Ndel1 results in desmosome defects in the epidermis. Our data thus identify Ndel1 as a desmosome-associated protein which promotes local assembly/organization of keratin filaments and is essential for both robust cell adhesion and epidermal barrier function.

cell biology↗