# Cadherin Clusters and actin filaments

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $462,306

## Abstract

Cadherin clustering is a unique molecular process that mediates and controls cell-cell adhesion. In
addition, it also regulates the actin cytoskeleton, polarity, proliferation, and apparently other structures
and signaling pathways. Cadherin clusters reinforce weak individual adhesive bonds and generate
functional cell-cell adhesion links. By connecting to F-actin, they determine the overall organization
and dynamics of the actin cytoskeleton. Finally, they provide specific structural scaffolds for various
signaling pathways. Despite such incredibly important functions, which obviously play out in nearly
every aspect of tissue morphogenesis, the molecular mechanisms and regulation of cadherin
clustering remains to be studied. This proposal will shed light on how cadherin clusters form and how
they participate in such diverse array of cellular mechanisms.
The work done under this proposal in previous years showed that adherens junctions (AJs), the major
cell-cell adhesion structures in vertebrates, consist of numerous transient but highly adhesive
cadherin nanoclusters. The short lifetime of each cluster makes AJs adhesive and flexible at the same
time. The continuous generation of these clusters is apparently based on a remarkable reaction –
cooperative binding of the cadherin-associated protein α-catenin to actin filaments. The assembly-
disassembly cycles of both cadherin clusters and associated F-actin are tightly coupled thereby
synchronizing cadherin and actin dynamics in adjacent cells. Finally, we found that cadherin clusters
could be structurally diversified by cadherin/catenin-bound proteins. Diversification of cadherin
clustering is based on the fact that each of these proteins provides specific modes of lateral cadherin-
cadherin interactions. A variety of these interactions results in formation of an array of distinct clusters
each of which might have particular functions. The advances in understanding cadherin clustering
allow us to come up with this proposal, which includes: (i) the role of cadherin in clustering and
function of two proteins, signaling protein Erbin, and adaptor protein PLEKHA5; (ii) molecular
mechanisms interconnecting extracellular cadherin binding events with α-catenin-binding to F-actin;
and (iii) the role of cadherin clustering in some examples of tissue morphogenesis.

## Key facts

- **NIH application ID:** 10366391
- **Project number:** 2R01AR070166-06A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Sergey M Troyanovsky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $462,306
- **Award type:** 2
- **Project period:** 2016-07-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10366391

## Citation

> US National Institutes of Health, RePORTER application 10366391, Cadherin Clusters and actin filaments (2R01AR070166-06A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10366391. Licensed CC0.

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