Molecular constituents and phosphorylation‐dependent regulation of the post‐synaptic density

I. Introduction 267 II. Isolation of the PSD 267 III. Molecular Properties of PSD Constituents 269A. Glutamate Receptors 269B. CaM Kinase II and Protein Kinases 269C. Scaffold and Receptor‐Clustering Molecules 272D. Association Proteins and Adaptor Proteins 272E. Cytoskeletal Proteins 273F. Enzymes 273G. Proteins of Other Classes 273H. Proteins of Other Fractions 274 IV. Identification of PSD Proteins Based on Mass Spectrometry 274 V. Substrates of Protein Kinases 274A. CaM Kinase II Substrates 274B. PKA and PKC Substrates 275C. Substrates of MAP Kinase Cascade Kinases 275D. Src Family Kinase Substrates 276 VI. Regulation of PSD Proteins by Phosphorylation‐Dephosphorylation 276A. NMDA Receptor 277B. AMPA and Kainate Receptors 278C. Metabotropic Glutamate Receptors (mGluRs) 279D. CaM Kinase II 279E. K + ‐Channel Proteins 280F. Scaffold‐ and Adaptor‐Proteins 280G. nNOS 280H. Dynamin 281I. Membrane Proteins 281 VII. Perspectives 281 VIII. Conclusions 282 Abbreviations 282 References 282The post‐synaptic density (PSD) contains receptors with associated signaling‐ and scaffolding‐proteins that organize signal‐transduction pathways near the post‐synaptic membrane. The PSD plays an important role in synaptic plasticity, and protein phosphorylation is critical to the regulation of PSD function, including learning and memory. Recently, studies have investigated the protein constituents of the PSD and substrate proteins for various protein kinases by proteomic analysis. The present review focuses on the molecular properties of PSD proteins, and substrates of protein kinases and their regulation by phosphorylation in order to understand the role of PSD in synaptic plasticity. © 2003 Wiley Periodicals, Inc., Mass Spec Rev 21:266–286, 2002; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/mas.10033