Molecular Mechanisms of Dendritic Spine Plasticity in Development and Aging
The postsynaptic density (PSD) of spinous excitatory synapses is characterized by an electron-dense filamentous meshwork of cytoskeletal proteins that serve three major functions: (1) the organization of glutamate receptors, (2) the clustering of synaptic
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Molecular Mechanisms of Dendritic Spine Plasticity in Development and Aging
M. R. Kreutz . I. Ko¨nig . M. Mikhaylova . C. Spilker . W. Zuschratter
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246 2 The Structure of Dendritic Spine Synapses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246 3 The Postsynaptic Density of the Spinous Synapse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247 4 Synaptogenesis and the Formation of Dendritic Spine Synapses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250 5 Molecular Dynamics of the Plastic Spine or What are Spines Good for . . . . . . . . . . . . . . . . . . . . . . . . . 251 6 Molecular Mechanisms of Spine Plasticity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253 7 Structural Alterations of Spine Number and Formation in Brain Disease States . . . . . . . . . . . . . . . 254 8 The Dendritic Spine in the Aging Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254
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2008 Springer ScienceþBusiness Media, LLC.
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Molecular mechanisms of dendritic spine plasticity in development and aging
Abstract: The postsynaptic density (PSD) of spinous excitatory synapses is characterized by an electron‐ dense filamentous meshwork of cytoskeletal proteins that serve three major functions: (1) the organization of glutamate receptors, (2) the clustering of synaptic adhesion molecules, and (3) the coupling of synaptic membrane proteins to intracellular signaling cascades. Consequently, in recent years a plethora of protein– protein interactions of PSD scaffolding proteins has been mapped and their possible function for the formation and integrity of the synapse delineated. It is assumed that structural alterations in the PSD precede morphological alterations of the spine. Detailed studies of such processes are of particular significance because they will probably lead to a new conceptual framework in our appreciation of how changes in the protein composition and protein–protein interactions in the PSD can regulate spine morphogenesis. This should provide novel answers to the long‐standing question—what molecular mechanisms underlie synaptic plasticity and in turn learning and memory processes? List of Abbreviations: AKAP79, A‐kinase anchor protein 79; CaMKII, calcium/calmodulin‐dependent protein kinase II; CNS, central nervous system; GAP, GTPase‐activating protein; GEF, guanine nucleotide exchange factors; LTD, long‐term depression; LTP, long‐term potentiation; NCAM, neural cell adhesion molecule; PAK, p21‐activated kinase; PSD, postsynaptic density; SER, smooth endoplasmic reticulum; SynCAM, synaptic cell adhesion molecule
1 Introduction Synapses are sites of
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