# Roles for desmsomes in mRNA localization and translational regulation

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $551,685

## Abstract

Abstract
Desmosomes are cell adhesion structures that provide mechanical stability to the epidermis and
other tissues. Their canonical function is to link cells to the underlying intermediate filament
network, and disruption of these linkages can lead to diverse pathologies including skin blistering
and cardiomyopathies/dysplasias. For example, in autoimmune diseases collectively known as
pemphigus, pathogenic antibodies targeting the desmosomes result in life-threatening blistering
and loss of barrier function. We have identified a novel role for desmosomes in organizing the
localization of mRNAs in the cell, as well as the localization of translational machinery and
regulators. Further, perturbing desmosomes through wounding or through treatment with
pathogenic pemphigus antibody disrupts the desmosome-dependent localization of translational
regulators to the cell cortex. Based on these data, we propose that desmosomes are major
regulators of mRNA and translational pathways. Additionally, we hypothesize that desmosomes
are sensors of tissue integrity that alter translation in response to defective adhesion. Here we will
determine the molecular mechanisms underlying cortical recruitment of mRNAs and translational
regulators. Further, to define the functional relevance of translational control by desmosomes, we
will determine the acute translational response upon desmosome disruption during both wounding
and pemphigus. In addition, we will use single molecule live-imaging approaches to determine the
sites of protein translation under both homeostatic conditions and when desmosomes are
disrupted. This work will define novel mechanisms for cell adhesions in regulating post-
transcriptional gene expression, which may have essential functions in sensing and responding to
defects in epithelial integrity.

## Key facts

- **NIH application ID:** 10975976
- **Project number:** 1R01AR083352-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Terry H Lechler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $551,685
- **Award type:** 1
- **Project period:** 2024-08-16 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10975976

## Citation

> US National Institutes of Health, RePORTER application 10975976, Roles for desmsomes in mRNA localization and translational regulation (1R01AR083352-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10975976. Licensed CC0.

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