Cadherin clusters and actin filaments

钙粘蛋白粘附的显著特征之一是其可塑性。这一特点在正常情况下至关重要。 和病理性组织重塑这个项目的长期目标是确定如何基于钙粘蛋白 粘附结合了将细胞保持在一起的力量和允许快速粘附的可塑性。 细胞间接触的重组。 我们最近的结果，在这个建议中概述，提出了一个概念上的新模型的粘附 连接组件和功能。我们提出了强有力的证据表明， 钙粘蛋白相关蛋白α-catenin与肌动蛋白丝连接，不断产生钙粘蛋白簇 由细胞质膜上的数百个分子组成。这些的主要特点 集群的另一个特点是它们是短暂的，不一定参与反式相互作用。在同一 同时，它们是高度粘附的，因为它们的粘附界面被细胞内肌动蛋白加强， 脚手架我们认为，这种短暂的，但高度粘附的集群可能是基础的 粘附连接可塑性，允许细胞在形态发生过程中重新调整它们的连接。 我们的初步数据表明，这些集群，它们的形成，动力学和结构特征， 可以使用先进的成像技术，如TIRF显微镜，斑点荧光 显微镜、单分子定位显微镜和铂复制电子显微镜。在 结合生物物理测量和点诱变，我们将确定肌动蛋白如何 细丝使用这些高度粘附的钙粘蛋白簇来控制细胞间粘附。

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.