Considerable evidence indicates the crucial role of Shank and Homer proteins in neuroplasticity, as well as alcohol and drug dependence.83–89 Shank and the Homer scaffolding proteins are located deeper within the PSD than the MAGUKs (i.e., toward the cytoplasm).70 Three genes encode for Shank proteins (Shank1, Shank2, and Shank3) and Shank scaffolding proteins bind to neuroligins and neurexins, as well as NMDAR complexes in the PSD.70 Shanks are capable of binding other scaffolding molecules within the PSD (e.g., Homers) and thus are capable of linking mGlu receptors, as well as AMPA and kainate ionotropic receptors to NMDARs. Therefore, scaffolding proteins present in the PSD mediate a number of plasticity-associated events through reorganization of PSD-associated proteins, regulation of membrane protein trafficking and activity, as well as the maintenance of associated epithelial cell polarity and morphology.90–92 Moreover, the connection between Shank proteins and neuroligins/neur-exins indicates that the PSD may bridge with the “active zone” of the presynaptic terminal. The Homer family of scaffolding proteins is encoded by 3 genes (Homer1, Homer2, and Homer3). Homer scaffolding proteins interact with the C-terminus of Group
