Regulation of EGF‐Stimulated EGF Receptor Endocytosis During M Phase

It has been generally accepted that endocytosis is inhibited during mitotic phase (M phase) as a means to insulate the cell from outside influences. Many endocytic/trafficking proteins are present during M phase, but are associated with partners that are distinct from those involved in trafficking pathways. These findings have led to the 'moonlighting' hypothesis. However, all these findings are based on the study of fluid-phase and constitutive endocytosis. Here, we used epidermal growth factor receptor (EGFR) as a model system to study ligand-induced receptor endocytosis in M phase. We found that EGF-induced EGFR endocytosis still occurs during M phase, but follows different kinetics. EGF-induced EGFR endocytosis is delayed/inhibited for a few minutes and is slower in M phase, especially at metaphase. However, consistent with previous reports, transferrin endocytosis is inhibited under the same conditions. We further showed that EGFR endocytosis is differentially regulated during the cell cycle: dependent on EGFR kinase activation in M phase, but independent of EGFR kinase activation in interphase. We conclude that cells have adopted a system for selective endocytosis in M phase.