Adherens Junction Dynamics

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Search this pathway for protein information from PhosphoSitePlus^®, our expert-curated knowledge base of protein phosphorylation and other post-translational modifications.

Pathway Description:

Adherens junctions are dynamic structures that form, strengthen and spread, degrade and then re-form as their associated proteins create ephemeral connections with counterparts from adjacent cells. This view updates the traditional model of a stable complex composed of cadherin, β-catenin, α-catenin bound to the actin cytoskeleton. Although cadherin does exist in a complex with β-catenin and α-catenin, this cadherin-catenin complex does not associate with the actin cytoskeleton. α-catenin does not directly anchor cell adhesion proteins to the actin cytoskeleton but acts as a regulatory protein to control actin filament dynamics.

Monomeric α-catenin binds β-catenin at adherens junctions and upon release forms α-catenin dimers that promote actin bundle formation. The transition from branched actin networks to bundled actin filaments correlates with the creation of mature, strong adherens junctions and a decrease in membrane lamellipodia. The connection between cell junctions and the cytoskeleton may be more dynamic than originally considered and may rely on multiple, weak associations between the cadherin-catenin complex and the actin cytoskeleton or rely on other membrane-associated proteins (i.e. nectin and afadin).

As with most dynamic cellular systems, a collection of kinases, phosphatases, and adaptor proteins regulate the activity and localization of a few key effector proteins. p120 catenin (δ-catenin) binds and stabilizes cadherin at the plasma membrane. Membrane-bound and cytosolic tyrosine kinases phosphorylate β-catenin at weak or nascent junctions, while phosphatases remove added phosphates from β-catenin and δ-catenin at established junctions. Rho family GTPases modulate the availability and activation state of catenins and other essential adherens proteins. Together, this collection of structural proteins, enzymes, and adaptor proteins create dynamic cell-cell junctions necessary for temporary associations during morphogenesis and maintains the integrity of complex tissues and structures following development.

Selected Reviews:

• Drees F, Pokutta S, Yamada S, Nelson WJ, Weis WI (2005) Alpha-catenin is a molecular switch that binds E-cadherin-beta-catenin and regulates actin-filament assembly. Cell 123(5), 903–15.
• Fox DT, Peifer M (2007) Cell adhesion: separation of p120's powers? Curr. Biol. 17(1), R24–7.
• Gates J, Peifer M (2005) Can 1000 reviews be wrong? Actin, alpha-Catenin, and adherens junctions. Cell 123(5), 769–72.
• Niessen CM, Gottardi CJ (2008) Molecular components of the adherens junction. Biochim. Biophys. Acta 1778(3), 562–71.
• Perez-Moreno M, Fuchs E (2006) Catenins: keeping cells from getting their signals crossed. Dev. Cell 11(5), 601–12.
• Yap AS, Crampton MS, Hardin J (2007) Making and breaking contacts: the cellular biology of cadherin regulation. Curr. Opin. Cell Biol. 19(5), 508–14.

We would like to thank Prof. Rakesh Kumar and Mona Motwani of The George Washington University, Washington, D.C. for reviewing this diagram.