Skip to main content
SpringerLink
Log in

The postsynaptic density

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Glutamatergic synapses in the central nervous system are characterized by an electron-dense web underneath the postsynaptic membrane; this web is called the postsynaptic density (PSD). PSDs are composed of a dense network of several hundred proteins, creating a macromolecular complex that serves a wide range of functions. Prominent PSD proteins such as members of the MaGuk or ProSAP/Shank family build up a dense scaffold that creates an interface between clustered membrane-bound receptors, cell adhesion molecules and the actin-based cytoskeleton. Moreover, kinases, phosphatases and several proteins of different signalling pathways are specifically localized within the spine/PSD compartment. Small GTPases and regulating proteins are also enriched in PSDs being the molecular basis for regulated structural changes of cytoskeletal components within the synapse in response to external or internal stimuli, e.g. synaptic activation. This synaptic rearrangement (structural plasticity) is a rapid process and is believed to underlie learning and memory formation. The characterization of synapse/PSD proteins is especially important in the light of recent data suggesting that several mental disorders have their molecular defect at the synapse/PSD level.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig.  5

Similar content being viewed by others

References

  • Abbott MA, Wells DG, Fallon JR (1999) The insulin receptor tyrosine kinase substrate p58/53 and the insulin receptor are components of CNS synapses. J Neurosc 19:7300–7308

    CAS  Google Scholar 

  • Adam G, Matus A (1996) Role of actin in the organisation of brain postsynaptic densities. Brain Res Mol Brain Res 31:246–250

    Article  Google Scholar 

  • Apperson ML, Moon IS, Kennedy MB (1996) Characterization of densin-180, a new brain-specific synaptic protein of the O-sialoglycoprotein family. J Neurosci 16:6839–6852

    PubMed  CAS  Google Scholar 

  • Bamji SX (2005) Cadherins: actin with the cytoskeleton to form synapses. Neuron 21:175–178

    Article  CAS  Google Scholar 

  • Baron MK, Boeckers TM, Vaida B, Faham S, Gingery M, Sawaya MR, Salyer D, Gundelfinger ED, Bowie JU (2006) An architectural framework that may lie at the core of the postsynaptic density. Science 311:531–555

    Article  PubMed  CAS  Google Scholar 

  • Belichenko PV, Masliah E, Kleschevnikov AM, Villar AJ, Epstein CJ, Salehi A, Mobley WC (2004) Synaptic structural abnormalities in the Ts65Dn mouse model of Down syndrome. J Comp Neurol 13:281–298

    Article  Google Scholar 

  • Bockers TM, Mameza MG, Kreutz MR, Bockmann J, Weise C, Buck F, Richter D, Gundelfinger ED, Kreienkamp HJ (2001) Synaptic scaffolding proteins in rat brain. Ankyrin repeats of the multidomain Shank protein family interact with the cytoskeletal protein alpha-fodrin. J Biol Chem 276:40104–40112

    Article  PubMed  CAS  Google Scholar 

  • Bockmann J, Kreutz MR, Gundelfinger ED, Böckers TM (2002) ProSAP/Shank postsynaptic density proteins interact with insulin receptor tyrosine kinase substrate IRSp53. J Neurochem 83:1013–1017

    Article  PubMed  CAS  Google Scholar 

  • Boeckers TM, Kreutz MR, Winter C, Zuschratter W, Smalla KH, Sanmarti-Vila L, Wex H, Langnaese K, Bockmann J, Garner CC, Gundelfinger ED (1999) Proline-rich synapse-associated protein-1/cortactin binding protein 1 (ProSAP1/CortBP1) is a PDZ-domain protein highly enriched in the postsynaptic density. J Neurosci 19:6506–6518

    PubMed  CAS  Google Scholar 

  • Boeckers TM, Bockmann J, Kreutz MR, Gundelfinger ED (2002) ProSAP/Shank proteins—a family of higher order organizing molecules of the postsynaptic density with an emerging role in human neurological disease. J Neurochem 81:903–910

    Article  PubMed  CAS  Google Scholar 

  • Boeckers TM, Liedtke Th, Dresbach Th, Bockmann J, Kreutz MR, Gundelfinger ED (2005) C-terminal synaptic targeting elements for postsynaptic density proteins ProSAP1/Shank2 and ProSAP2/Shank3. J Neurochem 92:519–524

    Article  PubMed  CAS  Google Scholar 

  • Bonaglia MC, Giorda R, Borgatti R, Felisari G, Gagliardi C, Selicorni A, Zuffardi O (2001) Disruption of the ProSAP2 gene in at (12;22)(q24.1;q13.3) is associated with the 22q13.3 deletion syndrome. Am J Hum Genet 69:261–268

    Article  PubMed  CAS  Google Scholar 

  • Brakeman PR, Lanahan AA, O’Brien R, Roche K, Barnes CA, Huganir RL, Worley PF (1997) Homer: a protein that selectively binds metabotropic glutamate receptors. Nature 386:284–288

    Article  PubMed  CAS  Google Scholar 

  • Brenman JE, Chao DS, Gee SH, McGee AW, Craven SE, Santillano DR, Wu Z, Huang F, Xia H, Peters MF, Froehner SC, Bredt DS (1996) Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains. Cell 84:757–767

    Article  PubMed  CAS  Google Scholar 

  • Bruckner K, Pablo Labrador J, Scheiffele P, Herb A, Seeburg PH, Klein R (1999) EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomains. Neuron 22:511–524

    Article  PubMed  CAS  Google Scholar 

  • Burkhardt C, Muller M, Badde A, Garner CC, Gundelfinger ED, Puschel AW (2005) Semaphorin 4B interacts with the post-synaptic density protein PSD-95/SAP90 and is recruited to synapses through a C-terminal PDZ-binding motif. FEBS Lett 579:3821–3828

    Article  PubMed  CAS  Google Scholar 

  • Carlin RK, Grab DJ, Cohen RS, Siekevitz P (1980) Isolation and characterization of postsynaptic densities from various brain regions: enrichment of different types of postsynaptic densities. J Cell Biol 86:831–845

    Article  PubMed  CAS  Google Scholar 

  • Carlin RK, Bartelt DC, Siekevitz P (1983) Identification of fodrin as a major calmodulin-binding protein in postsynaptic density preparations. J Cell Biol 96:443–448

    Article  PubMed  CAS  Google Scholar 

  • Carlisle HJ, Kennedy MB (2005) Spine architecture and synaptic plasticity. Trends in Neurosci 28:182–187

    Article  CAS  Google Scholar 

  • Carr DW, Stofko-Hahn RE, Fraser ID, Cone RD, Scott JD (1992) Localization of the cAMP-dependent protein kinase to the postsynaptic densities by A-kinase anchoring proteins. Characterization of AKAP 79. J Biol Chem 25:16816–16823

    Google Scholar 

  • Carroll RC, Beattie EC, Xia H, Luscher C, Altschuler Y, Nicoll RA, Malenka RC, Zastrow M von (1999) Dynamin-dependent endocytosis of ionotropic glutamate receptors. Proc Natl Acad Sci USA 96:14112–14117

    Article  PubMed  CAS  Google Scholar 

  • Chen L, Chetkovich DM, Petralia RS, Sweeney NT, Kawasaki Y, Wenthold RJ, Bredt DS, Nicoll RA (2000) Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms. Nature 408:936–943

    Article  PubMed  CAS  Google Scholar 

  • Chen X, Vinade L, Leapman RD, Petersen JD, Nakagawa T, Phillips TM, Sheng M, Reese TS (2005) Mass of the postsynaptic density and enumeration of three key molecules. Proc Natl Acad Sci USA 102:11551–11556

    Article  PubMed  CAS  Google Scholar 

  • Cheng D, Hoogenraad CC, Rush J, Ramm E, Schlager MA, Duong DM, Xu P, Rukshan S, Hanfelt J, Nakagawa T, Sheng M, Peng J (2006) Relative and absolute quantification of postsynaptic density proteome isolated from rat forebrain and cerebellum. Mol Cell Proteomics 5:1158–1170

    Article  PubMed  CAS  Google Scholar 

  • Cho KO, Hunt CA, Kennedy MB (1992) The rat brain postsynaptic density fraction contains a homolog of the Drosophila discs-large tumor suppressor protein. Neuron 9:929–942

    Article  PubMed  CAS  Google Scholar 

  • Collins MO, Husi H, Yu L, Brandon JM, Anderson CN, Blackstock WP, Choudhary JS, Grant SG (2006) Molecular characterization and comparison of the components and multiprotein complexes in the postsynaptic proteome. J Neurochem (in press)

  • Craven SE, Bredt DS (1998) PDZ proteins organize synaptic signaling pathways. Cell 93:495–498

    Article  PubMed  CAS  Google Scholar 

  • De Robertis E, Bennett HS (1954) Submicroscopic vesicular component in the synapse. Fed Proc 13:35–42

    Google Scholar 

  • Dong H, O’Brien RJ, Fung ET, Lanahan AA, Worley PF, Huganir RL (1997) GRIP: a synaptic PDZ domain containing protein that interacts with AMPA receptors. Nature 386:279–284

    Article  PubMed  CAS  Google Scholar 

  • Dosemeci A, Reese TS (1993) Inhibition of endogenous phosphatase in a postsynaptic density fraction allows extensive phosphorylation of the major postsynaptic density protein. J Neurochem 61:550–555

    Article  PubMed  CAS  Google Scholar 

  • Ehlers MD, Zhang S, Bernhadt JP, Huganir RL (1996) Inactivation of NMDA receptors by direct interaction of calmodulin with the NR1 subunit. Cell 8:745–755

    Article  Google Scholar 

  • Farr CD, Gafken PR, Norbeck AD, Doneanu CE, Stapels MD, Barofsky DF, Minami M, Saugstad JA (2004) Proteomic analysis of native metabotropic glutamate receptor 5 protein complexes reveals novel molecular constituents. J Neurochem 91:438–450

    Article  PubMed  CAS  Google Scholar 

  • Fiala JC, Spacek J, Harris KM (2002) Dendritic spine pathology: cause or consequence of neurological disorders? Brain Res Brain Res Rev 39:29–54

    Article  PubMed  Google Scholar 

  • Fifkova E, Morales M (1992) Actin matrix of dendritic spines, synaptic plasticity, and long-term potentiation. Int Rev Cytol 139:267–307

    Article  PubMed  CAS  Google Scholar 

  • Foster M (1897) A text book of physiology (7th edn). Macmillan, New York

    Google Scholar 

  • Fukata Y, Tzingounis AV, Trinidad JC, Fukata M, Burlingame AL, Nicoll RA, Bredt DS (2005) Molecular constituents of neuronal AMPA receptors. J Cell Biol 9:399–404

    Article  CAS  Google Scholar 

  • Funke L, Dokoji S, Bredt DS (2005) Membrane associated guanylate kinases regulate adhesion and plasticity at cell junctions. Annu Rev Biochem 74:219–245

    Article  PubMed  CAS  Google Scholar 

  • Garcia EP, Mehta S, Blair LA, Wells DG, Shang J, Fukushima T, Fallon JR, Garner CC, Marshall J (1998) SAP90 binds and clusters kainate receptors causing incomplete desensitization. Neuron 21:727–739

    Article  PubMed  CAS  Google Scholar 

  • Garcia RA, Vasudevan K, Buonanno A (2000) The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses. Proc Natl Acad Sci USA 28:3596–3601

    Article  Google Scholar 

  • Garner CC, Nash J, Huganir RL (2000) PDZ domains in synapse assembly and signalling. Trends Cell Biol 10:274–280

    Article  PubMed  CAS  Google Scholar 

  • Giese KP, Fedorov NB, Filipkowski RK, Silva AJ (1998) Autophosphorylation at Thr286 of the alpha calcium calmodulin kinase II in LTP and learning. Science 279:870–873

    Article  PubMed  CAS  Google Scholar 

  • Grab DJ, Berzins K, Cohen RS, Siekevitz P (1979) Presence of calmodulin in postsynaptic densities isolated from canine cerebral cortex. J Biol Chem 10:8690–8696

    Google Scholar 

  • Groc L, Gustafsson B, Hanse E (2006) AMPA signalling in nascent glutamatergic synapses: there and not there! Trends Neurosci 29:132–139

    Article  PubMed  CAS  Google Scholar 

  • Gundelfinger ED, Boeckers TM, Baron M, Bowie JU (2006) A role for zinc in synapse asSAMbly? Trends Biol Sci (in press)

  • Harris BZ, Lim WA (2001) Mechanism and role of PDZ domains in signaling complex assembly. J Cell Sci 114:3219–3231

    PubMed  CAS  Google Scholar 

  • Hering H, Sheng M (2001) Dendritic spines: structure, dynamics and regulation. Nat Rev Neurosci 2:880–888

    Article  PubMed  CAS  Google Scholar 

  • Hollmann M, Heinemann S (1994) Cloned glutamate receptors. Annu Rev Neurosci 17:31–118

    Article  PubMed  CAS  Google Scholar 

  • Hori K, Yasuda H, Konno D, Maruoka H, Tsumoto T, Sobue K (2005) NMDA receptor-dependent synaptic translocation of insulin receptor substrate p53 via protein kinase C signaling. J Neurosci 9:2670–2681

    Article  CAS  Google Scholar 

  • Husi H, Grant SGN (2001) Isolation of 2000-kDa complexes of N-methyl-D-aspartate receptor and postsynaptic density 95 from mouse brain. J Neurochem 77:281–291

    Article  PubMed  CAS  Google Scholar 

  • Husi H, Ward MA, Choudhary JS, Blackstock WP, Grant SG (2000) Proteomic analysis of NMDA receptor-adhesion protein signaling complexes. Nat Neurosci 3:661–669

    Article  PubMed  CAS  Google Scholar 

  • Hwang JI, Kim HS, Lee JR, Kim E, Ryo SH, Suh PG (2005) The interaction of phospholipase Cβ3 with Shank2 regulates mGluR-mediated calcium signal. J Biol Chem 280:12467–12473

    Article  PubMed  CAS  Google Scholar 

  • Inanobe A, Fujita A, Ito M, Tomoike H, Inageda K, Kurachi Y (2002) Inward rectifier K+ channel Kir2.3 is localized at the postsynaptic membrane of excitatory synapses. Am J Physiol Cell Physiol 282:C1396–C1403

    PubMed  CAS  Google Scholar 

  • Irie M, Hata Y, Takeuchi M, Ichtchenko K, Toyoda A, Hirao K, Takai Y, Rosahl TW, Sudhof TC (1997) Binding of neuroligins to PSD-95. Science 277:1511–1515

    Article  PubMed  CAS  Google Scholar 

  • Irwin SA, Patel B, Idupulapati M, Harris JB, Crisostomo RA, Larsen BP, Kooy F, Willems PJ, Cras P, Kozlowski PB, Swain RA, Weiler IJ, Greenough WT (2001) Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am J Med Genet 15:161–167

    Article  Google Scholar 

  • Kammermeier PJ (2006) Surface clustering of metabotropic glutamate receptor 1 induced by long Homer proteins. BMC Neurosci 4:7–11

    Google Scholar 

  • Kammermeier PJ, Xiao B, Tu JC, Worley PF, Ikeda SR (2000) Homer proteins regulate coupling of group I metabotropic glutamate receptors to N-type calcium and M-type potassium channels. J Neurosci 20:7238–7245

    PubMed  CAS  Google Scholar 

  • Kaufmann WE, Moser HW (2000) Dendritic anomalies in disorders associated with mental retardation. Cereb Cortex 10:981–991

    Article  PubMed  CAS  Google Scholar 

  • Kawabe H, Hata Y, Takeuchi M, Ide N, Mizoguchi A, Takai Y (1999) nArgBP2, a novel neural member of ponsin/ArgBP2/vinexin family that interacts with synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP). J Biol Chem 274:30914–30918

    Article  PubMed  CAS  Google Scholar 

  • Kennedy MB (1997) The postsynaptic density at glutamatergic synapses. Trends Neurosci 20:264–268

    Article  PubMed  CAS  Google Scholar 

  • Kennedy MB (2000) Signal-processing machines at the postsynaptic density. Science 290:750–754

    Article  PubMed  CAS  Google Scholar 

  • Kennedy MB, Bennett MK, Erondu NE (1983) Biochemical and immunochemical evidence that the “major postsynaptic density protein” is a subunit of a calmodulin-dependent protein kinase. Proc Natl Acad Sci USA 80:7357–7361

    Article  PubMed  CAS  Google Scholar 

  • Kim E, Sheng M (2004) PDZ domain proteins of synapses. Nat Rev Neurosci 5:771–781

    Article  PubMed  CAS  Google Scholar 

  • Kim E, Niethammer M, Rothschild A, Jan YN, Sheng M (1995) Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases. Nature 378:85–88

    Article  PubMed  CAS  Google Scholar 

  • Kim E, Naisbitt S, Hsueh YP, Rao A, Rothschild A, Craig AM, Sheng M (1997) GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules. J Cell Biol 136:669–678

    Article  PubMed  CAS  Google Scholar 

  • Kim JH, Liao D, Lau LF, Huganir RL (1998) SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family. Neuron 20:683–691

    Article  PubMed  CAS  Google Scholar 

  • Kim TW, Wu K, Xu JL, Black IB (1992) Detection of dystrophin in the postsynaptic density of rat brain and deficiency in a mouse model of Duchenne muscular dystrophy. Proc Natl Acad Sci USA 89:11642–11644

    Article  PubMed  CAS  Google Scholar 

  • Kim TW, Wu K, Xu JL, McAuliffe G, Tanzi RE, Wasco W, Black IB (1995) Selective localization of amyloid precursor-like protein 1 in the cerebral cortex postsynaptic density. Brain Res Mol Brain Res 32:36–44

    Article  PubMed  CAS  Google Scholar 

  • Kindler S, Rehbein M, Classen B, Richter D, Bockers TM (2004) Distinct spatiotemporal expression of SAPAP transcripts in the developing rat brain: a novel dendritically localized mRNA. Brain Res Mol Brain Res 126:14–21

    Article  PubMed  CAS  Google Scholar 

  • Kistner U, Wenzel BM, Veh RW, Cases-Langhoff C, Garner AM, Appeltauer U, Voss B, Gundelfinger ED, Garner CC (1993) SAP90, a rat presynaptic protein related to the product of the Drosophila tumor suppressor gene dlg-A. J Biol Chem 5:4580–4583

    Google Scholar 

  • Klauck TM, Scott JD (1995) The postsynaptic density: a subcellular anchor for signal transduction enzymes. Cell Signal 7:747–757

    Article  PubMed  CAS  Google Scholar 

  • Kneussel M (2005) Postsynaptic scaffold proteins at non-synaptic sites. The role of postsynaptic scaffold proteins in motor-protein-receptor complexes. EMBO Rep 6:22–27

    Article  PubMed  CAS  Google Scholar 

  • Kone BC, Kuncewicz T, Zhang W, Yu ZY (2003) Protein interactions with nitric oxide synthases: controlling the right time, the right place, and the right amount of nitric oxide. Am J Physiol Renal Physiol 285:F178–F190

    PubMed  CAS  Google Scholar 

  • Kornau HC, Schenker LT, Kennedy MB, Seeburg PH (1995) Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science 22:1737–1740

    Article  Google Scholar 

  • Kornau HC, Seeburg PH, Kennedy MB (1997) Interaction of ion channels and receptors with PDZ domain proteins. Curr Opin Neurobiol 7:368–373

    Article  PubMed  CAS  Google Scholar 

  • Kreienkamp HJ, Zitzer H, Gundelfinger ED, Richter D, Bockers TM (2000) The calcium-independent receptor for alpha-latrotoxin from human and rodent brains interacts with members of the ProSAP/SSTRIP/Shank family of multidomain proteins. J Biol Chem 275:32387–32390

    Article  PubMed  CAS  Google Scholar 

  • Langnaese K, Seidenbecher C, Wex H, Seidel B, Hartung K, Appeltauer U, Garner A, Voss B, Mueller B, Garner CC, Gundelfinger ED (1996) Protein components of a rat brain synaptic junctional protein preparation. Brain Res Mol Brain Res 42:118–122

    Article  PubMed  CAS  Google Scholar 

  • Leonard AS, Davare MA, Horne MC, Garner CC, Hell JW (1998) SAP97 is associated with the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit. J Biol Chem 273:19518–19524

    Article  PubMed  CAS  Google Scholar 

  • Leyland ML, Dart C (2004) An alternatively spliced isoform of PSD-93/chapsyn 110 binds to the inwardly rectifying potassium channel, Kir2.1. J Biol Chem 279:43427–43436

    Article  PubMed  CAS  Google Scholar 

  • Li KW, Hornshaw MP, Van Der Schors RC, Watson R, Tate S, Casetta B, Jimenez CR, Gouwenberg Y, Gundelfinger ED, Smalla KH, Smit AB (2004) Proteomics analysis of rat brain postsynaptic density. Implications of the diverse protein functional groups for the integration of synaptic physiology. J Biol Chem 279:987–1002

    Article  PubMed  CAS  Google Scholar 

  • Li KW, Hornshaw MP, Minnen J van, Smalla KH, Gundelfinger ED, Smit AB (2005) Organelle proteomics of rat synaptic proteins: correlation-profiling by isotope-coded affinity tagging in conjunction with liquid chromatography-tandem mass spectrometry to reveal post-synaptic density specific proteins. J Proteome Res 4:725–733

    Article  PubMed  CAS  Google Scholar 

  • Liao D, Zhang X, O’Brien R, Ehlers MD, Huganir RL (1999) Regulation of morphological postsynaptic silent synapses in developing hippocampal neurons. Nat Neurosci 2:37–43

    Article  PubMed  CAS  Google Scholar 

  • Lim S, Sala C, Yoon J, Park S, Kuroda S, Sheng M, Kim E (2001) Sharpin, a novel postsynaptic density protein that directly interacts with the shank family of proteins. Mol Cell Neurosci 17:385–397

    Article  PubMed  CAS  Google Scholar 

  • Lin JW, Ju W, Foster K, Lee SH, Ahmadian G, Wyszynski M, Wang YT, Sheng M (2000) Distinct molecular mechanisms and divergent endocytotic pathways of AMPA receptor internalization. Nat Neurosci 3:1282–1290

    Article  PubMed  CAS  Google Scholar 

  • Lüscher C, Nicoll RA, Malenka RC, Muller D (2000) Synaptic plasticity and dynamic modulation of the postsynaptic membrane. Nat Neurosci 3:545–550

    Article  PubMed  Google Scholar 

  • Ma XM, Huang J, Wang Y, Eipper BA, Mains RE (2003) Kalirin, a multifunctional Rho guanine nucleotide exchange factor, is necessary for maintenance of hippocampal pyramidal neuron dendrites and dendritic spines. J Neurosci 19:10593–10603

    Google Scholar 

  • Maruoka H, Konno D, Hori K, Sobue K (2005) Collaboration of PSD-Zip70 with its binding partner, SPAR, in dendritic spine maturity. J Neurosci 25:1421–1430

    Article  PubMed  CAS  Google Scholar 

  • Matus A (2000) Actin-based plasticity in dendritic spines. Science 290:754–758

    Article  PubMed  CAS  Google Scholar 

  • Mayer ML, Armstrong N (2004) Structure and function of glutamate receptor ion channels. Annu Rev Physiol 66:161–181

    Article  PubMed  CAS  Google Scholar 

  • McCool BA, Pin JP, Harpold MM, Brust PF, Stauderman KA, Lovinger DM (1998) Rat group I metabotropic glutamate receptors inhibit neuronal Ca2+ channels via multiple signal transduction pathways in HEK 293 cells. J Neurophysiol 79:379–391

    PubMed  CAS  Google Scholar 

  • Migaud M, Charlesworth P, Dempster M, Webster LC, Watabe AM, Makhinson M, He Y, Ramsay MF, Morris RG, Morrison JH, O’Dell TJ, Grant SG (1998) Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein. Nature 396:433–439

    Article  PubMed  CAS  Google Scholar 

  • Minakami R, Jinnai N, Sugiyama H (1997) Phosphorylation and calmodulin binding of the metabotropic glutamate receptor subtype 5 (mGluR5) are antagonistic in vitro. J Biol Chem 272:20291–20298

    Article  PubMed  CAS  Google Scholar 

  • Mizui T, Takahashi H, Sekino Y, Shirao T (2005) Overexpression of drebrin A in immature neurons induces the accumulation of F-actin and PSD-95 into dendritic filopodia, and the formation of large abnormal protrusions. Mol Cell Neurosci 30:630–638

    Article  PubMed  CAS  Google Scholar 

  • Naisbitt S, Kim E, Tu JC, Xiao B, Sala C, Valtschanoff J, Weinberg RJ, Worley PF, Sheng M (1999) Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. Neuron 23:569–582

    Article  PubMed  CAS  Google Scholar 

  • Nesslinger NJ, Gorski JL, Kurczynski TW, Shapira SK, Siegel-Bartelt J, Dumanski JP, Cullen RF, French BN, McDermid H (1994) Clinical, cytogenetic and molecular characterization of seven patients with deletions of chromosome 22q13.3. Am J Hum Genet 54:464–472

    PubMed  CAS  Google Scholar 

  • Neuhoff H, Sassoe-Pognetto M, Panzanelli P, Maas C, Witke W, Kneussel M (2005) The actin-binding protein profilin I is localized at synaptic sites in an activity-regulated manner. Eur J Neurosci 21:15–25

    Article  PubMed  Google Scholar 

  • Niethammer M, Kim E, Sheng M (1996) Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases. J Neurosci 16:2157–2163

    PubMed  CAS  Google Scholar 

  • Noel J, Ralph GS, Pickard L, Williams J, Molnar E, Uney JB, Collingridge GL, Henley JM (1999) Surface expression of AMPA receptors in hippocampal neurons is regulated by an NSF-dependent mechanism. Neuron 23:365–376

    Article  PubMed  CAS  Google Scholar 

  • Okamoto PM, Gamby C, Wells D, Fallon J, Vallee RB (2001) Dynamin isoform-specific interaction with the Shank/ProSAP scaffolding proteins of the postsynaptic density and actin cytoskeleton. J Biol Chem 276:48458–48465

    PubMed  CAS  Google Scholar 

  • Olson PA, Tkatch T, Hernandez-Lopez S, Ulich S, Ilijic E, Mugnaini E, Zhang H, Bezprozvanny I, Surmeier DJ (2005) G-protein coupled receptor modulation of striatal Cav1.3 L-type Ca2+ channels is dependent on a Shank-binding domain. J Neurosci 25:1050–1062

    Article  PubMed  CAS  Google Scholar 

  • Osterweil E, Wells DG, Mooseker MS (2005) A role for myosin VI in postsynaptic structure and glutamate receptor endocytosis. J Cell Biol 17:329–338

    Article  CAS  Google Scholar 

  • Pak DT, Yang S, Rudolph-Correia S, Kim E, Sheng M (2001) Regulation of dendritic spine morphology by SPAR, a PSD-95-associated RapGAP. Neuron 31:289–303

    Article  PubMed  CAS  Google Scholar 

  • Palade GE, Palay SL (1954) Electron microscope observations of interneuronal and neuromuscular syapses. Anat Rec 118:335–336

    Google Scholar 

  • Park E, Na M, Choi J, Kim S, Lee JR, Yoon J, Park D, Sheng M, Lim E (2003) The Shank family of postsynaptic density proteins interacts with and promotes synaptic accumulation of the βPix guanine nucleotide exchange factor for Rac1 and CDC42. J Biol Chem 278:19220–19229

    Article  PubMed  CAS  Google Scholar 

  • Peng J, Kim MJ, Cheng D, Duong DM, Gygi SP, Sheng M (2004) Semiquantitative proteomic analysis of rat forebrain postsynaptic density fractions by mass spectrometry. J Biol Chem 279:21003–21011

    Article  PubMed  CAS  Google Scholar 

  • Penzes P, Johnson RC, Alam MR, Kambampati V, Mains RE, Eipper BA (2000) An isoform of kalirin, a brain-specific GDP/GTP exchange factor, is enriched in the postsynaptic density fraction. J Biol Chem 3:6395–6403

    Article  Google Scholar 

  • Penzes P, Johnson RC, Sattler R, Zhang X, Huganir RL, Kambampati V, Mains RE, Eipper BA (2001) The neuronal Rho-GEF kalirin-7 interacts with PDZ domain-containing proteins and regulates dendritic morphogenesis. Neuron 29:229–242

    Article  PubMed  CAS  Google Scholar 

  • Penzes P, Beeser A, Chernoff J, Schiller MR, Eipper BA, Mains RE, Huganir RL (2003) Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin. Neuron 37:263–274

    Article  PubMed  CAS  Google Scholar 

  • Petralia RS, Sans N, Wang YX, Wenthold RJ (2005) Ontogeny of postsynaptic density proteins at glutamatergic synapses. Mol Cell Neurosci 29:436–452

    Article  PubMed  CAS  Google Scholar 

  • Prasad C, Prasad AN, Chordiker BN, Lee C, Dawson AK, Jocelyn LJ, Chudley AE (2000) Genetic evaluation of pervasive developmental disorders: the terminal 22q13 deletion syndrome may represent a recognizable phenotype. Clin Genet 57:103–109

    Article  PubMed  CAS  Google Scholar 

  • Qualmann B, Boeckers TM, Jeromin M, Gundelfinger ED, Kessels M (2004) Linkage of the actin cytoskeleton to the postsynaptic density via direct interactions of Abp1 with the ProSAP/Shank family. J Neurosci 24:2481–2495

    Article  PubMed  CAS  Google Scholar 

  • Quitsch A, Berhörster K, Liew CW, Richter D, Kreienkamp HJ (2005) Postsynaptic Shank antagonizes dendrite branching induced by leucine-rich repeat protein Densin 180. J Neurosci 25:479–487

    Article  PubMed  CAS  Google Scholar 

  • Racz B, Weinberg RJ (2004) The subcellular organization of cortactin in hippocampus. J Neurosci 17:10310–10317

    Article  CAS  Google Scholar 

  • Roussignol G, Ango F, Romorini S, Tu JC, Sala C, Worley PF, Bockaert J, Fagni L (2005) Shank expression is sufficient to induce functional dendritic spine synapses in aspiny neurons. J Neurosci 6:3560–3570

    Article  CAS  Google Scholar 

  • Sala C, Piech V, Wilson NR, Passafaro M, Liu G, Sheng M (2001) Regulation of dendritic spine morphology and synaptic function by Shank and Homer. Neuron 31:115–130

    Article  PubMed  CAS  Google Scholar 

  • Scheiffele P (2003) Cell-cell signaling during synapse formation in the CNS. Annu Rev Neurosci 26:485–508

    Article  PubMed  CAS  Google Scholar 

  • Schultze W, Eulenburg V, Lessmann V, Herrmann L, Dittmar T, Gundelfinger ED, Heumann R, Erdmann KS (2001) Semaphorin4F interacts with the synapse-associated protein SAP90/PSD-95. J Neurochem 78:482–489

    Article  PubMed  CAS  Google Scholar 

  • Schütz G, Rosário M, Grimm J, Boeckers TM, Gundelfinger ED, Birchmeier W (2004) The neuronal scaffold protein, Shank, mediates receptor tyrosine kinase signalling and biological function. J Cell Biol 167:945–952

    Article  CAS  Google Scholar 

  • Sheng M (2001) Molecular organization of the postsynaptic specialization. Proc Natl Acad Sci USA 19:7058–7061

    Article  Google Scholar 

  • Sheng M, Hyoung Lee S (2003) AMPA receptor trafficking and synaptic plasticity: major unanswered questions. Neurosci Res 46:127–134

    PubMed  CAS  Google Scholar 

  • Sheng M, Kim E (2000) The Shank family of scaffold proteins. J Cell Science 113:1851–1856

    PubMed  CAS  Google Scholar 

  • Sheng M, Sala C (2001) PDZ domains and the organization of supramolecular complexes. Annu Rev Neurosci 24:1–29

    Article  PubMed  CAS  Google Scholar 

  • Shi SH (2001) AMPA receptor dynamics and synaptic plasticity. Science 30:1851–1852

    Article  Google Scholar 

  • Shirao T, Sekino Y (2001) Clustering and anchoring mechanisms of molecular constituents of postsynaptic scaffolds in dendritic spines. Neurosci Res 40:1–7

    Article  PubMed  CAS  Google Scholar 

  • Silva AJ, Stevens CF, Tonegawa S, Wang Y (1992) Deficient hippocampal long-term potentiation in a calcium calmodulin kinase II mutant mice. Science 257:201–206

    Article  PubMed  CAS  Google Scholar 

  • Smith KE, Gibson ES, Dell’Acqua ML (2006) cAMP-dependent protein kinase postsynaptic localization regulated by NMDA receptor activation through translocation of an A-kinase anchoring protein scaffold protein. J Neurosci 1:2391–2402

    Article  CAS  Google Scholar 

  • Snyder EM, Colledge M, Crozier RA, Chen WS, Scott JD, Bear MF (2005) Role for A kinase-anchoring proteins (AKAPS) in glutamate receptor trafficking and long term synaptic depression. J Biol Chem 29:16962–16968

    Article  CAS  Google Scholar 

  • Soltau M, Richter D, Kreienkamp HJ (2002) The insulin receptor substrate IRSp53 links postsynaptic shank1 to the small G-protein CDC42. Mol Cell Neusosci 21:575–583

    Article  CAS  Google Scholar 

  • Song I, Kamboj S, Xia J, Dong H, Liao D, Huganir RL (1998) Interaction of the N-ethylmaleimide-sensitive factor with AMPA receptors. Neuron 21:393–400

    Article  PubMed  CAS  Google Scholar 

  • Song JY, Ichtchenko K, Sudhof TC, Brose N (1999) Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses. Proc Natl Acad Sci USA 96:1100–1105

    Article  PubMed  CAS  Google Scholar 

  • Spacek J, Harris KM (1997) Three-dimensional organization of smooth endoplasmic reticulum in hippocampal CA1 dendrites and dendritic spines of the immature and mature rat. J Neurosci 17:190–203

    PubMed  CAS  Google Scholar 

  • Sprengel R, Suchanek B, Amico C, Brusa R, Burnashev N, Rozov A, Hvalby O, Jensen V, Paulsen O, Andersen P, Kim JJ, Thompson RF, Sun W, Webster LC, Grant SG, Eilers J, Konnerth A, Li J, McNamara JO, Seeburg PH (1998) Importance of the intracellular domain of NR2 subunits for NMDA receptor function in vivo. Cell 23:279–289

    Article  Google Scholar 

  • Sugiyama Y, Kawabata I, Sobue K, Okabe S (2005) Determination of absolute protein numbers in single synapses by a GFP-based calibration technique. Nat Methods 2:677–684

    Article  PubMed  CAS  Google Scholar 

  • Suzuki T, Okumura-Noji K (1995) NMDA receptor subunits epsilon 1 (NR2A) and epsilon 2 (NR2B) are substrates for Fyn in the postsynaptic density fraction isolated from the rat brain. Biochem Biophys Res Commun 13:582–588

    Article  Google Scholar 

  • Suzuki T, Okumura-Noji K, Tanaka R, Ogura A, Nakamura K, Kudo Y, Tada T (1993) Characterization of protein kinase C activities in postsynaptic density fractions prepared from cerebral cortex, hippocampus, and cerebellum. Brain Res 13:69–75

    Article  Google Scholar 

  • Suzuki T, Okumura NK, Nishida E (1995) ERK2-type mitogen-activated protein kinase (MAPK) and its substrates in postsynaptic density fractions from the rat brain. Neurosci Res 22:277–285

    Article  PubMed  CAS  Google Scholar 

  • Suzuki T, Li W, Zhang JP, Tian QB, Sakagami H, Usuda N, Kondo H, Fujii T, Endo S (2005) A novel scaffold protein, TANC, possibly a rat homolog of Drosophila rolling pebbles (rols), forms a multiprotein complex with various postsynaptic density proteins. Eur J Neurosci 21:339–350

    Article  PubMed  Google Scholar 

  • Swann JW, Al-Noori S, Jiang M, Lee CL (2000) Spine loss and other dendritic abnormalities in epilepsy. Hippocampus 10:617–625

    Article  PubMed  CAS  Google Scholar 

  • Takeuchi M, Hata Y, Hirao K, Toyoda A, Irie M, Takai Y (1997) SAPAPs: a family of PSD-95/SAP90-associated proteins localized at postsynaptic density. J Biol Chem 272:11943–11951

    Article  PubMed  CAS  Google Scholar 

  • Thomas U (2002) Modulation of synaptic signalling complexes by Homer proteins. J Neurochem 81:407–413

    Article  PubMed  CAS  Google Scholar 

  • Togashi H, Abe K, Mizoguchi A, Takaoka K, Chisaka O, Takeichi M (2002) Cadherin regulates dendritic spine morphogenesis. Neuron 3:77–89

    Article  Google Scholar 

  • Tomita SM, Fukata RA, Nicoll RA, Bredt DS (2004) Dynamic interaction of stargazing-like TARPs with cycling AMPARs at synapses. Science 303:1508–1511

    Article  PubMed  CAS  Google Scholar 

  • Toni N, Buchs PA, Nikonenko I, Bron CR, Muller D (1999) LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite. Nature 25:421–425

    Google Scholar 

  • Tu JC, Xiao B, Yuan JP, Lanahan AA, Leoffert K, Li M, Linden DJ, Worley PF (1998) Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors. Neuron 21:717–726

    Article  PubMed  CAS  Google Scholar 

  • Tu JC, Xiao B, Naisbitt S, Yuan JP, Petralia RS, Brakeman P, Doan A, Aakalu VK, Lanahan AA, Sheng M, Worley PF (1999) Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins. Neuron 23:583–592

    Article  PubMed  CAS  Google Scholar 

  • Uchino S, Wada H, Honda S, Nakamura Y, Ondo Y, Uchiyama T, Tsutsumi M, Suzuki E, Hirasawa T, Kohsaka S (2006) Direct interaction of post-synaptic density-95/Dlg/ZO-1 domain-containing synaptic molecule Shank3 with GluR1 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor. J Neurochem 97:1203–1214

    Article  PubMed  CAS  Google Scholar 

  • Uemura T, Mori H, Mishina M (2004) Direct interaction of GluRδ2 with Shank scaffold proteins in cerebellar Purkinje cells. Mol Cell Neurosci 26:330–341

    Article  PubMed  CAS  Google Scholar 

  • Valtschanoff JG, Weinberg RJ (2001) Laminar organization of the NMDA receptor complex within the postsynaptic density. J Neurosci 21:1211–1217

    PubMed  CAS  Google Scholar 

  • Vazquez LE, Chen HJ, Sokolova I, Knuesel I, Kennedy MB (2004) SynGAP regulates spine formation. J Neurosci 24:8862–8872

    Article  PubMed  CAS  Google Scholar 

  • Walikonis RS, Jensen ON, Mann M, Provance DW Jr, Mercer JA, Kennedy MB (2000) Identification of proteins in the postsynaptic density fraction by mass spectrometry. J Neurosci 1:4069–4080

    Google Scholar 

  • Walsh MJ, Kuruc N (1992) The postsynaptic density: constituent and associated proteins characterized by electrophoresis, immunoblotting, and peptide sequencing. J Neurochem 59:667–678

    Article  PubMed  CAS  Google Scholar 

  • Watt JL, Olson IA, Johnston AW, Ross HS, Couzin DA, Stephen GS (1985) A familiar pericentric inversion of chromosome 22 with a recombinant subject illustrating a “pure” partial monosomy syndrome. J Med Genet 22:283–287

    Article  PubMed  CAS  Google Scholar 

  • Wendholt D, Spilker C, Schmitt A, Dolnik A, Smalla KH, Pröpper Ch, Bockmann J, Sobue K, Gundelfinger ED, Kreutz MR, Boeckers TM (2006) ProSAP interacting protein1 (ProSAPiP1), a novel postsynaptic density protein that links the spine associated Rap-Gap (SPAR) to the scaffolding protein ProSAP2/Shank3. J Biol Chem 281:13805–13816

    Article  PubMed  CAS  Google Scholar 

  • Wong ACC, Ning Y, Flint J, Clark K, Dumanski JP, Ledbetter DH, McDermid H (1997) Molecular characterization of a 130-Kb terminal microdeletion at 22q in a child with mild mental retardation. Am J Hum Genet 60:113–120

    PubMed  CAS  Google Scholar 

  • Xia J, Zhang X, Staudinger J, Huganir RL (1999) Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1. Neuron 22:179–187

    Article  PubMed  CAS  Google Scholar 

  • Xiao B, Tu JC, Worley PF (2000) Homer: a link between neural activity and glutamate receptor function. Cur Opin Neurobiol 10:370–374

    Article  CAS  Google Scholar 

  • Yuste R, Bonhoeffer T (2001) Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu Rev Neurosci 24:1071–1089

    Article  PubMed  CAS  Google Scholar 

  • Zhang H, Maximov A, Fu Y, Xu F, Tang TS, Tkatch T, Surmeier J, Bezprozvanny I (2005) Association of Cav1.3 L-type calcium channels with Shank. J Neurosci 25:1037–1049

    Article  PubMed  CAS  Google Scholar 

  • Ziff EB (1997) Enlightening the postsynaptic density. Neuron 19:1163–1174

    Article  PubMed  CAS  Google Scholar 

  • Zitzer H, Richter D, Kreienkamp HJ (1999) Agonist-dependent interaction of the rat somatostatin receptor subtype 2 with cortactin binding protein. J Biol Chem 274:18153–18156

    Article  PubMed  CAS  Google Scholar 

  • Zuber B, Nikonenko I, Klauser P, Muller D, Dubochet J (2005) The mammalian central nervous synaptic cleft contains a high density of periodically organized complexes. Proc Natl Acad Sci USA 102:19192–19197

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Ulm University, 89081, Ulm, Germany

    T. M. Boeckers

Authors
  1. T. M. Boeckers
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T. M. Boeckers.

Additional information

The work of former and current colleagues in my laboratory and the support with respect to research on components of the PSD network by the DFG (SFB497/B8, Bo1718/2-2) and by the Land Baden-Württemberg (1423/74) are gratefully acknowledged.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Boeckers, T.M. The postsynaptic density. Cell Tissue Res 326, 409–422 (2006). https://doi.org/10.1007/s00441-006-0274-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-006-0274-5

Keywords

Search

Navigation