Adherens Junction Pathway
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, and 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. Membranebound 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.
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We would like to thank Prof. Rakesh Kumar of The George Washington University, Washington, D.C. for reviewing this diagram.
created September 2008
revised November 2012