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

• Published in: Developmental cell 2021-04, Vol.56 (8), p.1131-1146.e3
• Main Authors: Sochacki, Kem A., Heine, Bridgette L., Haber, Gideon J., Jimah, John R., Prasai, Bijeta, Alfonzo-Méndez, Marco A., Roberts, Aleah D., Somasundaram, Agila, Hinshaw, Jenny E., Taraska, Justin W.
• Format: Article
• Language: English
• Subjects: Adhesiveness; Animals; Cell Line; Cell Membrane - physiology; Cell Membrane - ultrastructure; Cholesterol - metabolism; clathrin; Clathrin - metabolism; Cryoelectron Microscopy; endocytosis; Humans; Male; Mice; Models, Biological; plaques; platinum replica electron microscopy; Rats; tomography
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2021.03.017

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. •Flat clathrin lattices are common features in cells•Curved clathrin generally bends into a sphere while keeping a constant surface area•Flat clathrin can spontaneously curve without added energy, subunits, or factors•Flat clathrin is an irregular, loosely connected, pentagon-containing lattice Clathrin lattices are protein coats on the inside of the eukaryotic cell plasma membrane that internalize material into the cell. Sochacki et al. find that these geometric coats are commonly flat and can curve without added energy or factors. Their lattice structure may harbor the potential energy needed for curvature.