# Cadherin-catenin regulation in dividing epithelial cells

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $380,605

## Abstract

The cadherin-catenin cell-cell adhesion complex is essential for tissue development and homeostasis. While
the requirement of each component to intercellular adhesion has been long established, we know much less
about the structural and chemical modifications that regulate this complex. One barrier to understanding
cadherin/catenin adhesion regulation is the lack of a well-defined system for analysis. A second barrier is that
catenins serve functions outside of the cadherin-catenin complex, confounding loss of function analyses. Cells
dividing within an epithelium undergo stereotypic shape changes to separate the genome while also
maintaining the adhesive barrier, but how the cadherin-catenin complex might be regulated to accommodate
this essential process is unknown. We have generated a variant of α-catenin that shows enhanced binding F-
actin in vitro. CRISPR/Cas9-generated α-catenin knockout cells restored with this variant show a prominent
mitotic defect, particularly during cytokinesis. This shows that persistent coupling between α-catenin and F-
actin blocks cell division, and suggests that the α-catenin/F-actin interaction may be regulated during mitosis
(Aim 1). We've identified an evolutionarily conserved phosphorylation scheme in α-catenin that lies within a
linker region that joins the actin-binding and mechano-sensitive regions of α-catenin, each of which are
essential for α-catenin adhesive function in mammalian cells and flies. As this phosphorylation is upregulated
during mitosis, we hypothesize that α-catenin phosphorylation regulates cell division by altering the actin-
binding and/or mechanosensing property of α-catenin (Aim 2). Lastly, we've found that a form of α-catenin that
functions outside of the cadherin complex can bind phosphatidylinositol-3,4,5-trisphosphate (PIP3)-enriched
membranes and direct cortical actin organizations that might be relevant to mitotic division (Aim 3). Altogether,
this proposal incorporates skills from a multi-disciplinary team of collaborative investigators, using cell lines,
Drosophila, mechanical and biochemical approaches to address the fundamental question of how α-catenin is
structurally modified during mitosis, which will have broad implications for adhesion regulation across diverse
cell types.

## Key facts

- **NIH application ID:** 9959451
- **Project number:** 5R01GM129312-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Cara J Gottardi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $380,605
- **Award type:** 5
- **Project period:** 2018-09-20 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959451

## Citation

> US National Institutes of Health, RePORTER application 9959451, Cadherin-catenin regulation in dividing epithelial cells (5R01GM129312-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9959451. Licensed CC0.

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