# Actomyosin-dependent assembly of the mechanosensitive machinery from adherens junctions triggers actin polymerization and organization

**Authors:** Aurélie Favarin, Rayan Said, Hong Wang, Emilie Zeine, Amaury Pierrard, Julien Pernier, Hemalatha Narassimprakash, Stéphane Roméro, Alexis M. Gautreau, René-Marc Mège, Christophe Le Clainche

PMC · DOI: 10.1126/sciadv.ady4863 · Science Advances · 2026-01-01

## TL;DR

This study shows how cells use actomyosin forces to assemble proteins at cell junctions, which in turn organize actin filaments and reinforce cell connections.

## Contribution

The paper reveals a feedback loop where actomyosin contractility triggers mechanosensitive protein assembly, which then regulates actin polymerization and bundling.

## Key findings

- Actomyosin contractility alone triggers hierarchical assembly of α-catenin, vinculin, and VASP at adherens junctions.
- The α-catenin-vinculin-VASP complex promotes actin filament elongation and bundling while inhibiting Arp2/3-mediated branching.
- This machinery links mechanosensitive junctions to actin assembly and contractility in a self-reinforcing feedback loop.

## Abstract

Cells rely on cadherin-based adherens junctions (AJs) to form cohesive tissues. To establish contact, cells generate pushing forces through branched actin polymerization mediated by the actin-related protein 2/3 (Arp2/3) complex, followed by the reinforcement of mechanosensitive AJs in response to actomyosin contractility. To investigate how AJ proteins coordinate these events, we combined kinetic assays of actin polymerization, single actin filament observation in total internal reflection fluorescence microscopy, and in vitro reconstitution of AJ mechanosensitivity. Our findings show that actomyosin contractility alone is sufficient to trigger the hierarchical assembly of the AJ mechanosensitive proteins α-catenin, vinculin, and vasodilator-stimulated phosphoprotein (VASP). Once assembled, these proteins act synergistically to promote actin filament nucleation, elongation, and bundling. The α-catenin-vinculin-VASP machinery inhibits Arp2/3-mediated actin branching and instead promotes the myosin-dependent assembly of actin bundles. Together, these results reveal how AJs integrate actin assembly, actomyosin contractility, and mechanosensitivity in a feedback loop.

In vitro reconstitution shows how mechanosensitive adherens junction proteins link actomyosin contractility to actin assembly.

## Linked entities

- **Genes:** LOC110462068 (vinculin-like) [NCBI Gene 110462068], VASP (vasodilator stimulated phosphoprotein) [NCBI Gene 7408], ARP2_3 (Arp2/3 complex subunit, actin nucleation center) [NCBI Gene 19247154]
- **Proteins:** LOC110462068 (vinculin-like), MYH14 (myosin heavy chain 14)

## Full-text entities

- **Genes:** VCL (vinculin) [NCBI Gene 7414] {aka CMD1W, CMH15, HEL114, MV, MVCL, VINC}, VASP (vasodilator stimulated phosphoprotein) [NCBI Gene 7408], MYH14 (myosin heavy chain 14) [NCBI Gene 79784] {aka DFNA4, DFNA4A, FP17425, MHC16, MYH17, NMHC II-C}

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12757075/full.md

## References

75 references — full list in the complete paper: https://tomesphere.com/paper/PMC12757075/full.md

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Source: https://tomesphere.com/paper/PMC12757075