Cover legend: Confocal immunofluorescent image of two hippocampal neurons labeled for HA-tagged Nedd4-1, with and without AMPA treatment. In basal conditions (left), the E3 ubiquitin ligase Nedd4-1 is diffusely localized throughout the soma and dendrites. Upon activation of AMPA receptors (right), Nedd4-1 is rapidly recruited to excitatory synapses within dendritic spines, where it is able to ubiquitinate surface AMPA receptors and manipulate synaptic strength. For more details, see the article by Scudder et al. (pages 16637–16649).