Cadherin clusters and actin filaments

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One of the remarkable features of cadherin adhesion is its plasticity. This feature is crucial in normal and pathological tissue remodeling. The long-term goal of this project is to define how cadherin-based adhesion combines the strength that keeps cells together with the plasticity that allows for the fast restructuring of cell-cell contacts. Our recent results, outlined in this proposal, suggested a conceptually new model of adherens junction assembly and functioning. We present strong evidence that the cooperative binding of the cadherin-associated protein α-catenin to actin filaments continuously generates cadherin clusters consisting of hundreds of molecules on the cell plasma membrane. The major feature of these clusters is that they are short-lived and are not necessarily engaged in trans-interactions. At the same time, they are highly adhesive because their adhesive interface is reinforced by the intracellular actin scaffold. We propose that such transient, but highly adhesive clusters could be of the basis for the adherens junction plasticity, allowing cells to readjust their junctions during morphogenetic processes. Our preliminary data show that these clusters, their formation, dynamics, and structural characteristics can be studied using advanced imaging techniques such as TIRF microscopy, speckle fluorescent microscopy, single molecule localization microscopy, and platinum replica electron microscopy. In conjunction with biophysical measurements and point mutagenesis, we will determine how actin filaments use these highly adhesive cadherin clusters to manage intercellular adhesion.