Inter-junctional signaling in epithelial junctional complex

点击翻译按钮获取中文摘要

Abstract Each cell-cell contact integrates many individual junctions of several functionally and structurally different types. These junctions must be coordinately remodeled during morphogenetic changes. The long-term goal of our project is to define the mechanisms of this coordination. In the current funding cycle of our grant, we study the interplay between adhesive extracellular module and actin-binding intracellular module of adherens junctions (AJs). The cell-cell adhesion in these junctions is mediated by the transmembrane protein, cadherin, that interacts with the actin cytoskeleton through proteins called catenins. We discovered a remarkable binding process – the cooperative binding of α-catenin to actin filaments. We showed how this process controls the cadherin adhesive interface. In addition, the same process bundles actin filaments attached to AJs and the resulting bundles nucleate the assembly of another junctions, called nectin junctions (NJs). Our preliminary data suggests that this assembly is based on the specific recognition of the α-catenin-assembled bundles by the NJ protein, afadin. This and other data, outlined in our proposal, suggest a new hypothesis that the actin-binding proteins of NJs, tight junctions, and desmosomes recognize the local actin filament organization produced by AJs and that this recognition coordinates the assembly and dynamics of all junctions in the cell-cell contacts. Our proposal will not only explore this conceptually new type of cell signaling, but also will lay the foundation for understanding the role of this signaling in a complex morphogenetic process, keratinocyte stratification.