Adherens Junction Dynamics
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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. δ-catenin (p120 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 creates dynamic cell-cell junctions necessary for temporary associations during morphogenesis and maintains the integrity of complex tissues and structures following development.
Selected Reviews:
- Baum B, Georgiou M (2011) Dynamics of adherens junctions in epithelial establishment, maintenance, and remodeling. J. Cell Biol. 192(6), 907–17.
- Baumann K (2013) Cell cycle: Centralspindlin--the missing link. Nat. Rev. Mol. Cell Biol. 14(2), 68.
- Citi S, Spadaro D, Schneider Y, Stutz J, Pulimeno P (2011) Regulation of small GTPases at epithelial cell-cell junctions. Mol. Membr. Biol. 28(7-8), 427–44.
- Harris TJ, Tepass U (2010) Adherens junctions: from molecules to morphogenesis. Nat. Rev. Mol. Cell Biol. 11(7), 502–14.
- Niessen CM, Gottardi CJ (2008) Molecular components of the adherens junction. Biochim. Biophys. Acta 1778(3), 562–71.
- Niessen CM, Gottardi CJ (2008) Molecular components of the adherens junction. Biochim. Biophys. Acta 1778(3), 562–71.
- Yonemura S (2011) Cadherin-actin interactions at adherens junctions. Curr. Opin. Cell Biol. 23(5), 515–22.
We would like to thank Prof. Kris DeMali of The University of Iowa Carver College of Medicine, Iowa City, IA for reviewing this diagram.
created September 2008
revised August 2014