Endocytosis; of AMPA receptors and other postsynaptic cargo occurs at
endocytic zones (EZs), stably positioned sites of clathrin adjacent to
the postsynaptic density (PSD). The tight localization of postsynaptic
endocytosis is thought to control spine composition and regulate
synaptic transmission. However, the mechanisms that situate the EZ near
the PSD and the role of spine endocytosis in synaptic transmission are
unknown. Here, we report that a physical link between dynamin-3 and the
postsynaptic adaptor Homer positions the EZ near the PSD. Disruption of
dynamin-3 or its interaction with Homer uncouples the PSD from the EZ,
resulting in synapses lacking postsynaptic clathrin. Loss of the EZ
leads to a loss of synaptic AMPA receptors and reduced excitatory
synaptic transmission that corresponds with impaired synaptic
recycling. Thus, a physical link between the PSD and the EZ ensures
localized endocytosis and recycling by recapturing and maintaining a
proximate pool of cycling AMPA receptors.
