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Dynamic contacts: rearranging adherens junctions to drive epithelial remodelling

Key Points

  • Epithelial morphogenesis is regulated by the modulation of intercellular junctions, which are known as adherens junctions (AJs).

  • AJs comprise cadherin receptors and associated proteins, including actomyosin filaments.

  • The interactions between cadherins and actomyosin are mediated by α-catenin and vinculin (VCL) through complex mechanisms.

  • The control of AJ-associated actomyosin by small GTPases is important for maintaining and remodelling the AJ.

  • RHO-associated protein kinase (ROCK), an effector of RHO GTPases, induces the contraction of AJ-linked actomyosin networks, which leads to various forms of epithelial remodelling.

  • AJs are also modulated by other mechanisms, including cadherin turnover, sliding of the junctions and transcriptional control of junction regulators.

Abstract

Epithelial cells display dynamic behaviours, such as rearrangement, movement and shape changes, particularly during embryonic development and in equivalent processes in adults. Accumulating evidence suggests that the remodelling of cell junctions, especially adherens junctions (AJs), has major roles in controlling these behaviours. AJs comprise cadherin adhesion receptors and cytoplasmic proteins that associate with them, including catenins and actin filaments, and exhibit various forms, such as linear or punctate. Remodelling of AJs induces epithelial reshaping in various ways, including by planar-polarized apical constriction that is driven by the contraction of AJ-associated actomyosin and that occurs during neural plate bending and germband extension. RHO GTPases and their effectors regulate actin polymerization and actomyosin contraction at AJs during the epithelial reshaping processes.

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Figure 1: Molecular architecture of adherens junctions.
Figure 2: Structural details of adherens junctions.
Figure 3: Hypothetical differences between various cadherin-based cell–cell contacts.
Figure 4: Pathways to regulate actomyosin attachment to the cadherin–catenin complex.
Figure 5: Various forms of adherens junction modulation induce epithelial reshaping.

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Acknowledgements

The author thanks T. Nishimura for critical comments on the manuscript, K. Taguchi for editing the movie and S. Ito for suggestions on references. The author's laboratory is supported by the programme Grants-in-Aid for Specially Promoted Research of the Ministry of Education, Science, Sports and Culture of Japan.

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Correspondence to Masatoshi Takeichi.

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Supplementary information S1 (movie)

EPLIN stabilizes the ZA. Time-lapse images of DLD1 cells transfected with Kusabira Orange-tagged epithelial cadherin (E‑cadherin). Left, control cells; right, epithelial protein lost in neoplasm (EPLIN)-depleted cells. Frames were taken every minute for 20 minutes. Frame rate, 2.1 frames/s. Scale bar, 20 µm. Details of the experiments are described in REF. 1. Adherens junctions (AJs) in EPLIN-depleted cells are much more unstable and more mobile than those in wild-type cells, which suggests that EPLIN-mediated actin assembly is essential for the formation of the zonula adherens (ZA). © 2011 Taguchi et al. Journal of Cell Biology. 194:643–656. 10.1083/jcb.201104124. 1. Taguchi, K., Ishiuchi, T. & Takeichi, M. Mechanosensitive EPLIN-dependent remodeling of adherens junctions regulates epithelial reshaping. J. Cell Biol. 194, 643–656 (2011). (MOV 3128 kb)

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Glossary

Apical constriction

A process to induce the bending of epithelial sheets during various morphogenetic processes, such as gastrulation and neural tube formation. Epithelial cells shrink specifically at the apical ends in response to external or internal signals, and as a result their sheets bend towards the apical ends.

Zonula adherens

(ZA). A cell–cell adherens junction that forms a circumferential belt around the apical pole of epithelial cells.

Tight junctions

Circumferential rings at the apex of epithelial cells that seal adjacent cells to one another. Tight junctions regulate solute and ion flux between adjacent epithelial cells.

Desmosomes

Junctional structures that are formed by transmembrane proteins that are homologous to cadherins and are called desmocollins and desmogleins. These are linked to plakoglobin and desmoplakin, and are anchored to intermediate filaments.

Actomyosin cables

Subcellular structures that consist of accumulated actin filaments and myosin II. Sliding of myosin II motors along the actin filaments provides a force to contract the cables. These contracting cables have various roles in cell shape changes, which are dependent on where the cables are anchored.

Guanine nucleotide exchange factors

(GEFs). Proteins that facilitate the exchange of GDP for GTP in the nucleotide-binding pocket of a GTP-binding protein.

GTPase-activating proteins

(GAPs). Proteins that inactivate small GTP-binding proteins, such as RAS family members, by increasing their rate of GTP hydrolysis.

Planar cell polarity

A mechanism of cellular organization by which cells acquire information about their orientation within the tissue in the plane of the epithelium. It is distinct from apical–basal polarity.

Amnioserosa cells

Cells that form the amnioserosa, an extra-embryonic epithelial sheet that covers the dorsal side of fly embryos at the blastoderm stage.

Dorsal folds

Epithelial structures that form on the dorsal side of the gastrulating Drosophila melanogaster embryo. Dorsal epithelial sheets are folded at an anterior and posterior portion of the embryo during development. The anterior fold is shallower than the posterior fold.

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Takeichi, M. Dynamic contacts: rearranging adherens junctions to drive epithelial remodelling. Nat Rev Mol Cell Biol 15, 397–410 (2014). https://doi.org/10.1038/nrm3802

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