Adherens Junctions


Adherens junctions (AJs) are dynamic structures found in between cells that couple intercellular adhesion to the cytoskeleton thereby creating a transcellular network that coordinates the behaviour of a population of cells. Regulation of AJ formation and maintenance is crucial for cell shape, migration, morphogenesis and tissue homeostasis and repair. AJs not only regulate cell adhesion and cell shape but also form spatial landmarks for a variety of signalling complexes, thereby regulating other cellular functions next to adhesion.

Key concept:

  • AJs are essential for tissue integrity by coupling intercellular adhesion to the cytoskeleton.

  • AJ formation and maintenance requires the cooperative activity of two types of intercellular adhesive receptor complexes, the classical cadherin/catenin and nectin/afadin complexes.

  • Catenins provide cadherin‐mediated adhesion with a dynamic link to the cytoskeleton, regulate cadherin cell surface stability and couple AJs with signal pathways that regulate gene expression.

  • Cadherin‐mediated adhesion and the AJs proteins β‐catenin and p120ctn regulate the Wnt pathway important for cell fate and differentiation decisions.

  • AJs serve as spatially defined signal platforms by recruiting a range of signal transduction proteins. This is not only important for regulation of intercellular adhesive interactions and AJ stability but also allows for communication of cell surface changes to the nucleus.

  • The formation, maintenance and disassembly of AJs are regulated at different levels that involve rapid changes as well as indirect mechanisms that regulate gene expression.

  • The establishment of polarity is closely coupled to the formation of AJs.

  • Classical cadherins are essential for the formation of not only AJs but also desmosomes and tight junctions.

  • Alterations in AJ components directly contribute to human diseases, such as cancer and developmentally related syndromes.

  • AJs and human disease.

Keywords: intercellular junctions; adhesion; cadherins; nectins; Wnt signalling

Figure 1.

Schematic representation of the AJ. AJs consist of two distinct adhesive units: the calcium‐dependent classical cadherin/catenin complex and the calcium‐independent nectin/afadin complexes that both can interact with the actin cytoskeleton.

Figure 2.

Domain structure of the AJ core components. Bars indicate sites of protein interaction. IG, immunoglobulin‐like domain; Dil, dilute domain; EC, cadherin extracellular repeat; PDZ, PSD95/Dlg/ZO‐1 domain; RA, Ras association domain; FHA, Forkhead associated domain; VH, vinculin homology domain and PR, proline‐rich domain.

Figure 3.

Textbook model versus newer model for how the cadherin complex interacts with actin. In the text book model (old) the cadherin complex was directly bound to actin via α‐catenin. Recent data indicate that binding of α‐catenin to either β‐catenin or actin is mutually exclusive, resulting in a much more dynamic view on actin regulation by classical cadherins (new). In this model, actin binding either takes place in the vicinity of AJs through dynamic exchange of α‐catenin and binding is through other actin‐binding proteins that link α‐catenin to actin.

Figure 4.

Different mechanisms regulating AJ formation and maintenance. AJs are regulated on multiple levels ranging from regulation of gene expression, trafficking to posttranslational modification and proteolytic cleavage.

Figure 5.

Cadherins and catenins in the regulation of Wnt signalling. In the absence of Wnt β‐catenin is degraded on phosphorylation by the destruction complex (DC). Wnt binding to its receptors Frizzled inhibits the DC, resulting in accumulation and nuclear translocation of β‐catenin where it binds TCF/LEF transcription factors to activate Wnt‐dependent target genes. The interaction of p120ctn with the transcriptional repressor Kaiso, either in the cytoplasm or nucleus, relieves Kaiso repression of Wnt responsive genes, resulting in enhanced activation. Increased cadherin expression binds more β‐catenin and p120 resulting in a higher threshold for Wnt signalling, whereas loss of E‐cadherin may lower the threshold for Wnt/β‐catenin signalling. Reducing cadherin levels also releases p120 into the cytosol thereby further activating Wnt target genes. In addition, enhanced cadherin‐mediated adhesion promotes the activity of the membrane bound DC complex, reducing β‐catenin signal activity.



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Further Reading

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Yap AS, Crampton MS and Hardin J (2007) Making and breaking contacts: the cellular biology of cadherin regulation. Current Opinion in Cell Biology 19: 508–514.

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How to Cite close
Michels, Christian, and Niessen, Carien M(Mar 2010) Adherens Junctions. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020876]