Clathrin-mediated endocytosis—the process by which cells take up nutrients and signals within clathrin-coated vesicles—is very well understood. Kelly et al. reveal an unanticipated layer of regulation in this process. The proteins AP2 and clathrin are the major constituents of endocytic clathrin-coated vesicles. AP2 and clathrin stick together through a clathrin-binding motif in AP2. The authors now show that AP2’s clathrin-binding motif is normally buried within the core of the AP2 protein. AP2 only ejects its clathrin-binding motif and recruits clathrin if it is associated with the correct cell membrane and an endocytic cargo.
B. T. Kelly, S. C. Graham, N. Liska, P. N. Dannhauser, S. Höning, E. J. Ungewickell, D. J. Owen, AP2 controls clathrin polymerization with a membrane-activated switch. Science 345, 459–463 (2014). [Abstract] [Full Text]