Dynamics and nanoscale organization of the postsynaptic endocytic zone at excitatory synapses

ABSTRACT At postsynaptic sites of neurons, a prominent clathrin-coated structure, the endocytic zone (EZ), controls the trafficking of glutamate receptors and is essential for synaptic plasticity. Despite its importance, little is known about how this clathrin structure is organized to mediate endocytosis. We used live-cell and super-resolution microscopy techniques to reveal the dynamic organization of this poorly understood clathrin structure. We found that a subset of endocytic proteins only transiently appeared at postsynaptic sites. In contrast, other proteins, including Eps15, intersectin1L, and β2-adaptin, were persistently enriched and partitioned at the edge of the EZ. We found that uncoupling the EZ from the synapse led to the loss of most of these components, while disrupting the actin cytoskeleton or AP2-membrane interactions did not alter EZ positioning. We conclude that the EZ is a stable, highly organized molecular platform where components are differentially recruited and positioned to orchestrate the endocytosis of synaptic receptors.