title: A frontier in the understanding of synaptic plasticity: solving the structure of the postsynaptic density.
abstract: The postsynaptic density (PSD) is a massive multi-protein complex whose functions include positioning signalling molecules for induction of long-term potentiation (LTP) and depression (LTD) of synaptic strength. These processes are thought to underlie memory formation. To understand how the PSD coordinates bidirectional synaptic plasticity with different synaptic activation patterns, it is necessary to determine its three-dimensional structure. A structural model of the PSD is emerging from investigation of its molecular composition and connectivity, in addition to structural studies at different levels of resolution. Technical innovations including mass spectrometry of cross-linked proteins and super-resolution light microscopy can drive progress. Integrating different information relating to PSD structure is challenging since the structure is so large and complex. The reconstruction of a PSD subcomplex anchored by AKAP79 exemplifies on a small scale how integration can be achieved. With its entire molecular structure coming into focus, this is a unique opportunity to study the PSD.
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK. m.gold@ucl.ac.uk
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Gold
mesh_terms: D054758:A Kinase Anchor Proteins / Q000737:chemistry; D002462:Cell Membrane / Q000737:chemistry; D019295:Computational Biology; D018360:Crystallography, X-Ray / Q000379:methods; D006801:Humans; D017774:Long-Term Potentiation; D036881:Long-Term Synaptic Depression; D013058:Mass Spectrometry / Q000379:methods; D008958:Models, Molecular; D015394:Molecular Structure; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D009473:Neuronal Plasticity; D057907:Post-Synaptic Density / Q000737:chemistry*; D025941:Protein Interaction Mapping / Q000379:methods; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D054758:A Kinase Anchor Proteins; C487775:AKAP5 protein, human; D009419:Nerve Tissue Proteins; C033652:postsynaptic density proteins