Cell to Cell Heterogeneity of Clathrin Coat Dynamics Is Cell Cycle Dependent

Clathrin-mediated endocytosis (CME) is the most extensively studied trafficking pathway from the cell surface to membrane-bound organelles. Cells exhibit two major modes of endocytic clathrin coat formation: dynamic clathrin-coated pits and large, long-lived clathrin lattices called plaques. Even within monoclonal cell populations, there is significant cell-to-cell heterogeneity in the relative density of these distinct classes of clathrin coats and overall dynamics of CME. Using fluorescence live cell imaging and single particle tracking analysis, we observed significant variation in CME dynamics across different stages of the cell cycle. We also found that cell spreading area swayed significantly during interphase, negatively correlated with plaque density. Taken together with recently demonstrated cell cycle dependent alterations in directed migration, cytoskeletal rearrangement, adhesion remodeling and cell traction forces, these results provide important insights into the non-canonical functions of clathrin-coats. Our findings also suggest that conflicting observations regarding CME dynamics can be minimized by characterizing dynamic and structural properties of endocytic coats at different stages of the cell cycle.