Molecular Mobility-Mediated Regulation of E-Cadherin Adhesion

E-cadherin is a key membrane-localized receptor that mediates adhesion in epithelial tissues and enables mechanical tension sensing. Molecular mobility of E-cadherin on a cell membrane includes both diffusive motion as well as active transport such as those mediated by the actin cytoskeleton. Reduced membrane molecular mobility is necessary for E-cadherin clustering and adhesion formation. E-cadherin clustering results in sustained activation of mechanical signal transducer α-catenin at adhesions. An alteration in membrane physical properties or a change in E-cadherin–actin cytoskeletal interaction may alter E-cadherin molecular mobility, thereby altering the assembly of E-cadherin-mediated cell–cell adhesion in the absence of any changes in the levels of the protein. Cells in epithelial tissues utilize homotypic E-cadherin interaction-mediated adhesions to both physically adhere to each other and sense the physical properties of their microenvironment, such as the presence of other cells in close vicinity or an alteration in the mechanical tension of the tissue. These position E-cadherin centrally in organogenesis and other processes, and its function is therefore tightly regulated through a variety of means including endocytosis and gene expression. How does membrane molecular mobility of E-cadherin, and thus membrane physical properties and associated actin cytoskeleton, impinges on the assembly of adhesive clusters and signaling is discussed. Cells in epithelial tissues utilize homotypic E-cadherin interaction-mediated adhesions to both physically adhere to each other and sense the physical properties of their microenvironment, such as the presence of other cells in close vicinity or an alteration in the mechanical tension of the tissue. These position E-cadherin centrally in organogenesis and other processes, and its function is therefore tightly regulated through a variety of means including endocytosis and gene expression. How does membrane molecular mobility of E-cadherin, and thus membrane physical properties and associated actin cytoskeleton, impinges on the assembly of adhesive clusters and signaling is discussed. filamentous actin (F-actin)-based molecular assemblies that play a crucial role in determining the shape and physical structure of a cell, and that enable the development of cellular tension and mechanical signaling. also referred to as the zonula adherens or cell–cell junction, this is a molecular complex of E-cadherin and other proteins that forms at the interface of two apposing cells and connects the actin cytoskeleton in each of the adhering cells. a family of calcium-dependent, membrane-spanning adhesion proteins that mediate physical adhesions of neighboring cells in a variety of tissues, including epithelial tissues, through their biochemical interactions. a family of adaptor proteins, such as β- and α-catenin, that bind to cadherins and connect them to the actin cytoskeleton in adhering cells. the organized meshwork of locally secreted biomaterial consisting of various proteins including fibrous proteins such as collagen that enable cell adhesion; it provides signals for cellular growth, migration, and differentiation. finger-like, thin, F-actin-rich membrane protrusions that enable cells to probe their local environment. a family of membrane-spanning receptors that typically bind to ligands in the extracellular matrix on the extracellular side and to the cellular cytoskeleton on the intracellular side enabling cellular adhesion and sensing of mechanical properties of the extracellular environment. cellular signaling events that involve either the generation of mechanical tension through the cellular cytoskeleton and motor proteins or sensing of mechanical tension through structural alteration in signaling proteins. the random motion of molecules such as proteins in a medium such as the cell membrane or the cytosol that is dictated by the kinetic energy of the molecule, and that is dependent on its molecular properties, such as its mass, and on the properties of the medium, such as its viscosity. the cumulative motion of molecules such as proteins that includes both pure diffusion and active transport by cellular processes.