The postsynaptic density at glutamatergic synapses

The postsynaptic density (PSD) is a tiny, amorphous structure located beneath the postsynaptic membrane of synapses in the CNS. Until recently, the molecular composition and function of the PSD were mostly matters of speculation. With the advent of powerful new microchemical tools and molecular-genetic methods, three new classes of proteins have been identified in the PSD at glutamatergic synapses: the PSD-95 family, the NR2B subunit of the NMDA-type glutamate receptor, and densin-180. The PSD-95 family is involved in clustering of NMDA receptors. NR2B is phosphorylated by Ca2(+)-calmodulin-dependent protein kinase type II, a prominent constituent of the PSD. Densin-180 might represent a new class of synaptic adhesion molecule. Study of these molecules is beginning to reveal the functional significance of the PSD.

[1]  T. Reese,et al.  Differences in membrane structure between excitatory and inhibitory components of the reciprocal synapse in the olfactory bulb , 1974, The Journal of comparative neurology.

[2]  John H. Lewis,et al.  Crystal Structures of a Complexed and Peptide-Free Membrane Protein–Binding Domain: Molecular Basis of Peptide Recognition by PDZ , 1996, Cell.

[3]  B. Voss,et al.  SAP90, a rat presynaptic protein related to the product of the Drosophila tumor suppressor gene dlg-A. , 1993, The Journal of biological chemistry.

[4]  Y. Jan,et al.  Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases , 1995, Nature.

[5]  C. Cotman,et al.  PROTEINS OF THE POSTSYNAPTIC DENSITY , 1974, The Journal of cell biology.

[6]  Bostjan Kobe,et al.  Crystal structure of porcine ribonuclease inhibitor, a protein with leucine-rich repeats , 1993, Nature.

[7]  R. Liddington,et al.  Crystal structure of a PDZ domain , 1996, Nature.

[8]  D. Bredt,et al.  Interaction of Nitric Oxide Synthase with the Postsynaptic Density Protein PSD-95 and α1-Syntrophin Mediated by PDZ Domains , 1996, Cell.

[9]  J. Gurd Phosphorylation of the postsynaptic density glycoprotein gp180 by endogenous tyrosine kinase , 1985, Brain Research.

[10]  J. Deisenhofer,et al.  A structural basis of the interactions between leucine-rich repeats and protein ligands , 1995, Nature.

[11]  MB Kennedy,et al.  PSD-95 is associated with the postsynaptic density and not with the presynaptic membrane at forebrain synapses , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[12]  P. Seeburg The TINS/TiPS Lecture the molecular biology of mammalian glutamate receptor channels , 1993, Trends in Neurosciences.

[13]  P. Seeburg,et al.  Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. , 1995, Science.

[14]  Yu Tian Wang,et al.  Regulation of NMDA receptors by tyrosine kinases and phosphatases , 1994, Nature.

[15]  S. Nakanishi Molecular diversity of glutamate receptors and implications for brain function. , 1992, Science.

[16]  R. Huganir,et al.  SAP102, a Novel Postsynaptic Protein That Interacts with NMDA Receptor Complexes In Vivo , 1996, Neuron.

[17]  M. Colonnier Synaptic patterns on different cell types in the different laminae of the cat visual cortex. An electron microscope study. , 1968, Brain research.

[18]  E. Gundelfinger,et al.  Molecular characterization and spatial distribution of SAP97, a novel presynaptic protein homologous to SAP90 and the Drosophila discs-large tumor suppressor protein , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  J. Goldenring,et al.  Identification of the Major Postsynaptic Density Protein as Homologous with the Major Calmodulin‐Binding Subunit of a Calmodulin‐Dependent Protein Kinase , 1984, Journal of neurochemistry.

[20]  M. J. Walsh,et al.  The Postsynaptic Density: Constituent and Associated Proteins Characterized by Electrophoresis, Immunoblotting, and Peptide Sequencing , 1992, Journal of neurochemistry.

[21]  Peter J. Bryant,et al.  The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions , 1991, Cell.

[22]  M. Kennedy The postsynaptic density , 1993, Current Opinion in Neurobiology.

[23]  J. Gurd Phosphorylation of the Postsynaptic Density Glycoprotein gp 180 by Ca2+/Calmodulin‐Dependent Protein Kinase , 1985, Journal of neurochemistry.

[24]  M. Sheng,et al.  Heteromultimerization and NMDA Receptor-Clustering Activity of Chapsyn-110, a Member of the PSD-95 Family of Proteins , 1996, Neuron.

[25]  C. Cotman,et al.  ISOLATION OF POSTSYNAPTIC DENSITIES FROM RAT BRAIN , 1974, The Journal of cell biology.

[26]  J. Gurd,et al.  Tyrosine Phosphorylation in a Model of Ischemia Using the Rat Hippocampal Slice: Specific, Long‐Term Decrease in the Tyrosine Phosphorylation of the Postsynaptic Glycoprotein PSD‐GP180 , 1995, Journal of neurochemistry.

[27]  D. Bredt,et al.  Cloning and Characterization of Postsynaptic Density 93, a Nitric Oxide Synthase Interacting Protein , 1996, The Journal of Neuroscience.

[28]  M. Kennedy,et al.  Distinct forebrain and cerebellar isozymes of type II Ca2+/calmodulin-dependent protein kinase associate differently with the postsynaptic density fraction. , 1985, The Journal of biological chemistry.

[29]  M. Kennedy,et al.  Characterization of Densin-180, a New Brain-Specific Synaptic Protein of the O-Sialoglycoprotein Family , 1996, The Journal of Neuroscience.

[30]  James E. Vaughn,et al.  Review: Fine structure of synaptogenesis in the vertebrate central nervous system , 1989 .

[31]  C P Ponting,et al.  DHR domains in syntrophins, neuronal NO synthases and other intracellular proteins. , 1995, Trends in biochemical sciences.

[32]  P. Bryant,et al.  ZO-1, DlgA and PSD-95/SAP90: homologous proteins in tight, septate and synaptic cell junctions , 1993, Mechanisms of Development.

[33]  T. Soderling,et al.  A structural basis for substrate specificities of protein Ser/Thr kinases: primary sequence preference of casein kinases I and II, NIMA, phosphorylase kinase, calmodulin-dependent kinase II, CDK5, and Erk1 , 1996, Molecular and cellular biology.

[34]  J. Deisenhofer,et al.  The leucine-rich repeat: a versatile binding motif. , 1994, Trends in biochemical sciences.

[35]  P. Kelly,et al.  Synaptic proteins. Characterization of tubulin and actin and identification of a distinct postsynaptic density polypeptide , 1978, The Journal of cell biology.

[36]  S. Gomperts,et al.  Clustering Membrane Proteins: It's All Coming Together with the PSD-95/SAP90 Protein Family , 1996, Cell.

[37]  D. Cowburn Adaptors and integrators. , 1996, Structure.

[38]  D. Branton,et al.  Two independent domains of hDlg are sufficient for subcellular targeting: the PDZ1-2 conformational unit and an alternatively spliced domain , 1996, The Journal of cell biology.

[39]  M. Sheng,et al.  PDZs and Receptor/Channel Clustering: Rounding Up the Latest Suspects , 1996, Neuron.

[40]  M. Kennedy,et al.  Structure and regulation of type II calcium/calmodulin-dependent protein kinase in central nervous system neurons. , 1990, Cold Spring Harbor symposia on quantitative biology.

[41]  A. Matus,et al.  Brain postsynaptic densities: the relationship to glial and neuronal filaments , 1980, The Journal of cell biology.

[42]  A. Matus,et al.  Tubulin in postsynaptic junctional lattice , 1975, Nature.

[43]  Gray Eg Axo-somatic and axo-dendritic synapses of the cerebral cortex: An electron microscope study , 1959 .

[44]  C. Garner,et al.  Ultrastructural localization of Shaker-related potassium channel subunits and synapse-associated protein 90 to septate-like junctions in rat cerebellar Pinceaux. , 1996, Brain research. Molecular brain research.

[45]  P. De Camilli,et al.  Piccolo, a novel 420 kDa protein associated with the presynaptic cytomatrix. , 1996, European journal of cell biology.

[46]  M. Sheng,et al.  Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[47]  M. Kennedy Origin of PDZ (DHR, GLGF) domains. , 1995, Trends in biochemical sciences.

[48]  S. Harrison,et al.  Peptide–Surface Association: The Case of PDZ and PTB Domains , 1996, Cell.

[49]  James M. Anderson,et al.  Protein–protein interactions: PDZ domain networks , 1996, Current Biology.

[50]  M. Ginsberg,et al.  Platelet adhesion receptors. , 1995, Seminars in cell biology.

[51]  M. Kennedy,et al.  The rat brain postsynaptic density fraction contains a homolog of the drosophila discs-large tumor suppressor protein , 1992, Neuron.