From Pits to Plaques: Electron Microscopy Reveals Clathrin Structural Plasticity in Trafficking, Sorting and Adhesion

Clathrin-mediated trafficking has classically been described through the formation of curved clathrin-coated pits and vesicles. However, growing evidence indicates that clathrin assembles into a diverse array of membrane-associated architectures whose geometry, dynamics, and function vary across cellular compartments and physiological contexts. These include canonical coated pits at the plasma membrane and trans-Golgi network, extended flat lattices and plaques at the cell surface, clathrin coats associated with endosomal sorting domains, and tubular clathrin assemblies associated with three-dimensional migration. Here, we synthesize recent work, including cell-type-specific, mechanobiological, and ultrastructural studies, to propose clathrin structural plasticity as a core organizing principle of intracellular trafficking. We discuss how adaptor identity, membrane lipid composition, cytoskeletal coupling, and mechanical constraints collectively shape clathrin architectures, enabling a single coat system to support vesicular transport, cargo sorting, signaling, and adhesion.