Structural Insights into Ordered Multicomponent Assemblies in Cell Junctions

Cell junctions are essential structures of metazoan tissues that maintain cohesion and integrity and permit coordinated tissue rearrangements in development. Vertebrate junctions include stable structures, like adherens junctions, desmosomes, and focal adhesions, and transient, ultrastructurally less-defined complexes that mediate recognition and signaling. All are mediated by assemblies of cell adhesion and recognition proteins at the cell surface and cytoplasmic proteins that mediate signaling or linkage to the cytoskeleton. These multiple components must organize together to form large functional intercellular structures. Structural methods have provided deep insights into how these large structures assemble and revealed roles for intrinsic propensities of adhesion and recognition protein ectodomains to form ordered assemblies on membranes, often mirrored by their intracellular components. In this chapter, we discuss the structural and molecular principles underlying the assembly and organization of these large complexes and focus in detail on three important cadherin-mediated junctions: adherens junctions, desmosomes, and neuronal self-recognition complexes formed by clustered protocadherins. These examples highlight the highly specific and organized arrangements that contribute to junction assembly and how these mechanisms are closely tuned to the biological roles of specific junctions.