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Reference: Garner et al., Trends in Cell Biol. 10:274-280 (2000)
Synaptic junctions are highly specialized structures designed to promote the rapid and efficient transmission of signals from the presynaptic terminal to the postsynaptic membrane within the central nervous system. Proteins containing PDZ domains play a fundamental organizational role at both the pre- and postsynaptic plasma membranes. This review focuses on recent advances in our understanding of the mechanisms underlying the assembly of synapses in the central nervous system.
FIGURE 3. Schematic diagram of the protein–protein interactions between synaptic protein components of the postsynaptic density (PSD). Clustering and localization of postsynaptic glutamate receptors are thought to be mediated by several multidomain adaptor proteins. The best characterized of these are members of the SAP90/PSD-95 family of MAGUKs. The PDZ domains in SAP90/PSD-95 interact with the C-terminus of NMDA receptor subunits (NMDAR) and with the cell-adhesion molecule neuroligin. Kainate receptors (KainateR) interact with the Src homology 3 (SH3) domain of SAP90/PSD-95 by means of a PXXPR motif in their C-terminal tails. The guanylate kinase (GK) domain in SAP90/PSD-95 provides additional links to the postsynaptic cytoskeletal matrix by binding to GKAP. GKAP in turns binds through its C-terminal tail to the PDZ domain in ProSAP/Shank family members. ProSAP/Shank also contain several ankyrin (Ank) repeats, an SH3 domain, a SAM domain and a proline-rich region. The latter interacts with the EVH domains in Homer, which is a metabotropic glutamate receptor (mGluR)-binding protein, and also with the SH3 domain in the F-actin-binding protein cortactin. A final major component of the PSD is the protein GRIP/ABP, which contains seven PDZ domains and interacts with both AMPA receptors (AMPAR) and ephrin receptors (EPHR). How GRIP/ABP is tethered into this complex of scaffold proteins is currently unclear.
