Scaffolding Proteins at the Postsynaptic Density Shank as the Architectural Framework

H.-J. Kreienkamp

Contents

1 Scaffold Proteins of the Postsynaptic Density 366

2 Domain Structure of the Shank Proteins 367

3 Physiological Role of Shank Proteins 368

4 Molecular Interactions of Shank Scaffolds: Self Association 368

5 Molecular Interactions of Shank Scaffolds: Anchoring of Postsynaptic

Membrane Proteins 370

6 Molecular Interactions of Shank Scaffolds: Linkages to the Actin-Based

Cytoskeleton 372

7 Molecular Interactions of Shank Scaffolds: Signaling Proteins 373

8 Dynamic Regulation of PSD Scaffold Proteins at the Synapse 375

References 376

Abstract Shank proteins are multidomain scaffold proteins of the postsynaptic density, connecting neurotransmitter receptors and other membrane proteins with signaling proteins and the actin cytoskeleton. By virtue of their protein interactions, Shank proteins assemble signaling platforms for G-protein-mediated signaling and the control of calcium homeostasis in dendritic spines. In addition, they participate in morphological changes, leading to maturation of dendritic spines and synapse formation. The importance of the Shank scaffolding function is demonstrated by genetically determined forms of mental retardation, which may be caused by haploinsufficiency for the SHANK3 gene. Consistent with its central function within the postsynaptic density, the availability of Shank is tightly controlled by local synthesis and degradation, as well as actin-dependent dynamic rearrangements within the dendritic spine.

H.-J. Kreienkamp

Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52,

20246 Hamburg Germany

[email protected]

E. Klussmann, J. Scott (eds.) Protein-Protein Interactions as New Drug Targets. Handbook of Experimental Pharmacology 186, © Springer-Verlag Berlin Heidelberg 2008

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