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Adherens junctions: from molecules to morphogenesis

Nature Reviews Molecular Cell Biology volume 11, pages 502–514 (2010)Cite this article

Subjects

Key Points

  • Adherens junctions (AJs) meet the dual challenge of maintaining tissue architecture and facilitating cell movement during tissue development and renewal.

  • Across animal species, classic cadherins display diversity in the structure of their extracellular regions but share a conserved cytoplasmic tail and a common tendency to form clusters at the plasma membrane.

  • The cytoplasmic tail of classic cadherin binds to the catenins, which mediate links to cytoskeletal networks as well as exocytotic and endocytic machinery.

  • Crosstalk between cadherin–catenin clusters and actin regulators directs AJ assembly from initial cell–cell contacts.

  • Links between cadherin–catenin clusters and microtubules organize epithelial cells more globally.

  • Regulated endocytosis of cadherin–catenin clusters facilitates AJ remodelling.

  • The effects of cytoskeletal or endocytic regulation of AJs on overall tissue structure depends on whether the regulation occurs locally, at a subset of cell–cell contacts of individual cells, or globally, at all cell–cell contacts.

Abstract

How adhesive interactions between cells generate and maintain animal tissue structure remains one of the most challenging and long-standing questions in cell and developmental biology. Adherens junctions (AJs) and the cadherin–catenin complexes at their core are therefore the subjects of intense research. Recent work has greatly advanced our understanding of the molecular organization of AJs and how cadherin–catenin complexes engage actin, microtubules and the endocytic machinery. As a result, we have gained important insights into the molecular mechanisms of tissue morphogenesis.

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Figure 1: Electron micrograph of an AJ.
Figure 2: Evolution of classic cadherins.
Figure 3: Organization and cytoskeletal relationships of cadherin–catenin and nectin–afadin complexes.
Figure 4: Interplay between cadherin–catenin clusters and actin during AJ assembly and remodelling.
Figure 5: Interplay between cadherin–catenin clusters and microtubules.
Figure 6: Regulation of cadherin–catenin clusters by endocytosis.

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Acknowledgements

The authors thank A. Koehler for the image in Figure 1. Work on adherens junctions in the authors' laboratories is supported by the Natural Sciences and Engineering Research Counsel of Canada (to T.J.C.H.), the Canadian Institutes of Health Research (to T.J.C.H. and U.T.) and the Canadian Cancer Society (to U.T.). T.J.C.H. is a Canada research chair in cell polarity and animal development.

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  1. Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, M5S 3G5, Ontario, Canada

    Tony J. C. Harris & Ulrich Tepass

  2. Tony J. C. Harris & Ulrich Tepass

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Glossary

Bilateran

An animal with a bilaterally symmetrical body plan, such as humans, fish and insects.

Intermediate filament

A cytoskeletal filament that provides mechanical strength in higher eukaryotic cells.

Puncta adherenta

Cadherin–catenin clusters found at cell–cell contacts, often during early stages of AJ assembly.

Lamellipodium

A broad, flat protrusion at the leading edge of a moving cell that is enriched with a branched network of actin filaments.

LIM domain

A repeat of about 60 amino acids, including Cys and His residues, that is thought to be involved in protein–protein interactions.

Filopodium

A long, thin protrusion at the periphery of cells and growth cones. Filopodia are supported by F-actin bundles.

Guanine nucleotide exchange factor (GEF)

A protein that facilitates the exchange of guanine diphosphate (GDP) for guanine triphosphate (GTP) in the nucleotide-binding pocket of a GTP-binding protein.

Actomyosin

A complex of myosin and actin filaments that is responsible for contractility during a range of cellular movements in eukaryotic cells.

GTPase-activating protein

(GAP). A protein that stimulates the intrinsic ability of a GTPase to hydrolyse GTP to GDP. Therefore, GAPs negatively regulate GTPases by converting them from an active (GTP-bound) to an inactive (GDP-bound) state.

Microvillus

A small, finger-like projection that occurs on the exposed apical surfaces of epithelial cells. Microvilli are supported by F-actin bundles.

Clathrin-coated pit

The initial site of invagination of a clathrin-coated vesicle.

Notum

The dorsal side of the thorax of an adult insect.

Epithelial-to-mesenchymal transition

The transformation of epithelial cells into mesenchymal cells with migratory and invasive properties.

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Harris, T., Tepass, U. Adherens junctions: from molecules to morphogenesis. Nat Rev Mol Cell Biol 11, 502–514 (2010). https://doi.org/10.1038/nrm2927

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