# Actin Assembly at Cadherin Dependent Adherens Junctions

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $289,389

## Abstract

Project Summary.
We are interested in understanding how the actin cytoskeleton maintains cell-cell adhesion and
epithelial barrier function. Epithelial tissue is characterized by extensive cell-cell adhesive
contacts that organize the cells into cohesive sheets or tubes that separate two different
environments. E-cadherin is a cell-cell adhesion molecule necessary for the formation and
maintenance of many different epithelial sheets. Cadherin mediated cell-cell adhesion is actin
dependent, but we do not fully understand how actin contributes to cadherin adhesive function.
The prevailing model is that actomyosin dependent tensile forces stabilize cadherin dependent
cell-cell junctions, but this system by itself is not robust because small defects in adhesion
would tend to propagate and expand if myosin continued to pull on a ruptured junction. Cells
must have a back-up plan to maintain cell-cell adhesion and the epithelial barrier whenever
adhesive junctions break. We have identified CD2AP, EVL, and CRMP1 as three factors
necessary for assembling the actin cytoskeleton at cell-cell junctions. Depleting any of these
factors results in a precipitous drop in the amount of junctional actin and a loss of cell-cell
adhesion such that the epithelial sheet becomes perforated with holes. CD2AP, EVL, and
CRMP1 all modulate actin filament (+) end polymerization in vitro, and they are all necessary for
protrusive activity in migrating cells. Therefore, I hypothesize that the three factors direct actin
polymerization towards junctions to prevent them from spontaneously rupturing and to quickly
reseal them if the junctions should break. Consistent with our hypothesis, we have identified
novel populations of actin dependent protruding microspikes and small lamellipodia that form
continually at cell junctions in mature epithelial sheets that are no longer moving. Therefore,
actin polymerization continues to drive protrusive activity at cell-cell borders long after the cells
made contact, stopped moving, and built cell-cell adhesive junctions. The specific aims are to
1) identify the factors necessary for generating the protrusions at cell-cell junctions and identify
the underlying mechanisms, 2) test whether loss of cell-cell adhesion triggers actin assembly,
and 3) determine why loss of actin polymerization at cell-cell junctions leads to disruption of E-
cadherin organization and adhesive function. Results from this proposal could fundamentally
alter our current view of how actin helps maintain cell-cell adhesion while providing new
information as to why mutations in CD2AP lead to inherited kidney disease.

## Key facts

- **NIH application ID:** 9984404
- **Project number:** 5R01GM106106-07
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** William Brieher
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $289,389
- **Award type:** 5
- **Project period:** 2013-07-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984404

## Citation

> US National Institutes of Health, RePORTER application 9984404, Actin Assembly at Cadherin Dependent Adherens Junctions (5R01GM106106-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9984404. Licensed CC0.

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