Figure 1.
The model depicts AMPARs trafficking in dendritic spines. GluR2-containing AMPARs constitutively cycle within spines, regulated by proteins that directly bind to AMPARs. For example, a PDZ domain-containing protein GRIP stabilizes AMPARs on the surface and can be replaced by a PICK1-PKC complex that facilitates AMPAR internalization. Before endocytosis, AMPARs move laterally from the synaptic site to extrasynaptic regions, and then internalize. Constitutive cycling AMPARs may insert by exocytosis at extrasynaptic areas and then diffuse laterally to the synapse. NSF may play an important role in this process by freeing GluR2 from extrasynaptic membrane anchors (Gardner et al., 2005). How AMPARs are guided during diffusion is not clear. Diffusing AMPARs could also move out of the spines through the narrow spine neck. The diffusion rate of AMPARs is much slower at necks (shown by the red color) compared with the spine head (light blue). Spines without necks also show a relatively rapid diffusion rate. Therefore, the actin skeleton could regulate AMPAR lateral diffusion by altering the spine neck (shown as the double-headed arrow).