This is part of the Principal Investigator Seminar Series.
Cells need to respond to different types of stress, such as alterations in ion and nutrient concentration or viral infection. The plasma membrane acts as a critical interface for initiating an appropriate response to restore cellular homeostasis, and the primary mechanism by which mammalian cells control their plasma membrane proteome is clathrin-mediated endocytosis. However, the molecular mechanisms by which endocytic machinery incorporates extracellular inputs under different physiological conditions remain elusive. In my talk, I will focus on the role of two endocytic accessory proteins, which positively regulate global endocytic flux, FCHO2 and NECAP. Using super-resolution quantitative live-cell microscopy, we have revealed that both players affect distinct stages of transmembrane cargo internalization. Combined with structural and biochemical studies carried out by the group of D. Owen, we devised a model explaining how FCHO2 and NECAP orchestrate the formation of a clathrin-coated vesicle by sequentially acting on the central endocytic adaptor AP2.