# Function of Desmoglein 1/Pemphigus Foliaceus Antigen

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $454,654

## Abstract

The multi-layered epidermis provides an essential barrier against water loss, physical insults, and infection. Its
proper function requires that architectural features be polarized along its entire apical to basal axis (superficial
to deep layers). Contributing to the inherent tissue polarity of the epidermis are seven desmosomal cadherins,
whose differentiation-dependent arrangement is thought to have functional significance that transcends
intercellular adhesion. Indeed, our work during previous funding periods demonstrated that the cadherin
desmoglein 1 (Dsg1), which is first expressed as cells commit to differentiate and transit into the suprabasal
layers, acts as a scaffold that engages signaling mediators necessary for terminal differentiation. Its failure to
be expressed or properly exported to the plasma membrane disrupts organismal homeostasis in patients with
Severe dermatitis, Allergies and Metabolic wasting (SAM) syndrome, a syndrome we helped identify in 2013.
We hypothesize that Dsg1 coordinates two interrelated but distinct functions required for epidermal
morphogenesis: a biochemical program of differentiation, and cytoarchitectural changes required for
stratification to form the multi-layered tissue. The resulting tissue provides a protective, dynamic barrier
capable of sensing and responding to diverse mechanical and chemical stimuli. The specific objective of this
proposal is to determine how Dsg1 mediates changes in tissue architecture and signaling necessary for
morphogenesis. To fulfill this objective, we will use gain- and loss-of-function approaches in human 2- and 3D
cultures, human patient tissue, and knockout mouse models to address three aims: 1) We will define the
machinery that ensures the polarized distribution of Dsg1 in the epidermis, specifically, the extent to which
Dsg1 is delivered to the correct position on the plasma membrane through a microtubule minus end-directed
dynein-Tctex-Rab3D complex, requiring differentiation-dependent microtubule rearrangements. 2) We will
elucidate how Dsg1 modulates the mechanosensitive cortical cytoskeleton to control a temporary drop in
tension during formation of the first suprabasal cell layer, and then to concentrate tension in the granular layers
later in morphogenesis to ensure proper tight junction structure. 3) We will determine how Dsg1 works with
ErbB2 Interacting protein (Erbin) to promote epidermal differentiation by dampening Epidermal Growth Factor
Receptor (EGFR) signaling, through disrupting protein complexes permissive for EGFR signaling and/or
reducing EGFR mobility within the plasma membrane. These studies will reveal how Dsg1 coordinates
cytoarchitectural changes and signaling machinery required for epidermal differentiation, stratification, and
barrier formation, and will shed light on how interference with these functions contributes to inherited and
acquired skin diseases and cancer.

## Key facts

- **NIH application ID:** 10242767
- **Project number:** 5R01AR041836-29
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Kathleen Janee Green
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $454,654
- **Award type:** 5
- **Project period:** 1993-08-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242767

## Citation

> US National Institutes of Health, RePORTER application 10242767, Function of Desmoglein 1/Pemphigus Foliaceus Antigen (5R01AR041836-29). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242767. Licensed CC0.

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