# Inter-junctional signaling in epithelial junctional complex

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $455,855

## Abstract

Abstract
Each cell-cell contact integrates many individual junctions of several functionally and structurally different
types. These junctions must be coordinately remodeled during morphogenetic changes. The long-term
goal of our project is to define the mechanisms of this coordination.
In the current funding cycle of our grant, we study the interplay between adhesive extracellular module
and actin-binding intracellular module of adherens junctions (AJs). The cell-cell adhesion in these
junctions is mediated by the transmembrane protein, cadherin, that interacts with the actin cytoskeleton
through proteins called catenins. We discovered a remarkable binding process – the cooperative binding
of α-catenin to actin filaments. We showed how this process controls the cadherin adhesive interface. In
addition, the same process bundles actin filaments attached to AJs and the resulting bundles nucleate
the assembly of another junctions, called nectin junctions (NJs). Our preliminary data suggests that this
assembly is based on the specific recognition of the α-catenin-assembled bundles by the NJ protein,
afadin.
This and other data, outlined in our proposal, suggest a new hypothesis that the actin-binding proteins of
NJs, tight junctions, and desmosomes recognize the local actin filament organization produced by AJs
and that this recognition coordinates the assembly and dynamics of all junctions in the cell-cell contacts.
Our proposal will not only explore this conceptually new type of cell signaling, but also will lay the
foundation for understanding the role of this signaling in a complex morphogenetic process, keratinocyte
stratification.

## Key facts

- **NIH application ID:** 9989029
- **Project number:** 5R01AR044016-24
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Sergey M Troyanovsky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $455,855
- **Award type:** 5
- **Project period:** 1996-09-20 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989029

## Citation

> US National Institutes of Health, RePORTER application 9989029, Inter-junctional signaling in epithelial junctional complex (5R01AR044016-24). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989029. Licensed CC0.

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