Scaffold Proteins of the Postsynaptic Density

In the postsynaptic density (PSD) of excitatory (usually glutamatergic) synapses of the central nervous system, cell surface transmitter receptors are physically connected with components of their signal transduction machinery and the actin cytoskeleton. The PSD is usually located at the tip of dendritic protrusions of about 1-2 |im length, termed dendritic spines, separated from the presynaptic transmitter-containing terminal by the synaptic cleft (Fig. 1).

One of the hallmarks of the PSD is its size; hundred(s) of different proteins contribute to a large insoluble complex that accumulates a molecular weight of about 1.5 GDa (Chen et al. 2005). Thus, there is a strong need for scaffolds to keep this assembly together through various protein interaction motifs. Some of the scaffold proteins of the PSD, such as A-kinase anchoring proteins (AKAPs) or S-Scam/MAGI-proteins, are important in other large protein complexes; others, such as the SAP/PSD-95 family members, SAPAP/GKAPs, Homer and Shank proteins, are rather specific to the PSD of excitatory synapses. Here I will focus on the role of SH3- and ankyrin-containing proteins (Shank1-3; Naisbitt et al. 1999, also known as somatostatin receptor interacting protein, SSTRIP; Zitzer et al. 1999a; proline-rich synapse-associated protein, ProSAP;

Fig. 1 (a) Section of a dendrite from the mouse cerebral cortex, stained by the Golgi technique. Numerous dendritic spines are clearly visible. (b) Electron micrograph of a section from the mouse hippocampus. The PSD is visible as a black (i.e., electron dense) structure at the top of the spine. (c) Domain structure and possible splice variants of Shank proteins. Note that not all alternatively spliced inserts have been described for all three Shank genes fe) N

Fig. 1 (a) Section of a dendrite from the mouse cerebral cortex, stained by the Golgi technique. Numerous dendritic spines are clearly visible. (b) Electron micrograph of a section from the mouse hippocampus. The PSD is visible as a black (i.e., electron dense) structure at the top of the spine. (c) Domain structure and possible splice variants of Shank proteins. Note that not all alternatively spliced inserts have been described for all three Shank genes

Boeckers et al. 1999a; synamon, Yao et al. 1999; cortactin binding protein, CortBPl; Du et al. 1998) in the maturation, function and dynamics of postsynaptic specializations.

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