The structure and spontaneous curvature of clathrin lattices at the plasma membrane

Clathrin-mediated endocytosis is the primary pathway for receptor and cargo internalization in eukaryotic cells. It is characterized by a polyhedral clathrin lattice that coats budding membranes. The mechanism and control of lattice assembly, curvature, and vesicle formation at the plasma membrane has been a matter of long-standing debate. Here, we use platinum replica and cryoelectron microscopy and tomography to present a structural framework of the pathway. We determine the shape and size parameters common to clathrin-mediated endocytosis. We show that clathrin sites maintain a constant surface area during curvature across multiple cell lines. Flat clathrin is present in all cells and spontaneously curves into coated pits without additional energy sources or recruited factors. Finally, we attribute curvature generation to loosely connected and pentagon-containing flat lattices that can rapidly curve when a flattening force is released. Together, these data present a universal mechanistic model of clathrin-mediated endocytosis.

Automated summary

This study utilized platinum replica and cryoelectron microscopy and tomography to provide a structural framework of clathrin-mediated endocytosis and determined the shape and size parameters associated with this process. It was found that clathrin sites maintain a constant surface area during curvature and flat clathrin can spontaneously curve into coated pits without additional energy sources or recruited factors. The generation of curvature was attributed to loosely connected and pentagon-containing flat lattices that rapidly curve when a flattening force is released.