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The synaptic proteome

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Abstract

Synapses are focal hot spots for signal transduction and plasticity in the brain. A synapse comprises an axon terminus, the presynapse, the synaptic cleft containing extracellular matrix proteins as well as adhesion molecules, and the postsynaptic density as target structure for chemical signaling. The proteomes of the presynaptic and postsynaptic active zones control neurotransmitter release and perception. These tasks demand short- and long-term structural and functional dynamics of the synapse mediated by its proteinaceous inventory. This review addresses subcellular fractionation protocols and the related proteomic approaches to the various synaptic subcompartments with an emphasis on the presynaptic active zone (PAZ). Furthermore, it discusses major constituents of the PAZ including the amyloid precursor protein family members. Numerous proteins regulating the rearrangement of the cytoskeleton are indicative of the functional and structural dynamics of the pre- and postsynapse. The identification of protein candidates of the synapse provides the basis for further analyzing the interaction of synaptic proteins with their targets, and the effect of their deletion opens novel insights into the functional role of these proteins in neuronal communication. The knowledge of the molecular interactome is also a prerequisite for understanding numerous neurodegenerative diseases.

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Abbreviations

CAZ:

Cytomatrix assembled at the active zone

PAZ:

Presynaptic active zone

PPM:

Presynaptic plasma membrane

PSD:

Postsynaptic density

References

  • Anliker B, Muller U (2006) The functions of mammalian amyloid precursor protein and related amyloid precursor-like proteins. Neurodegener Dis 3:239–246

    CAS  PubMed  Google Scholar 

  • Bai F, Witzmann FA (2007) Synaptosome proteomics. Subcell Biochem 43:77–98

    PubMed Central  PubMed  Google Scholar 

  • Bajjalieh SM, Frantz GD, Weimann JM, McConnell SK, Scheller RH (1994) Differential expression of synaptic vesicle protein 2 (SV2) isoforms. J Neurosci 14:5223–5235

    CAS  PubMed  Google Scholar 

  • Barth J, Volknandt W (2011) Proteomic investigations of the synaptic vesicle interactome. Expert Rev Proteomics 8:211–220

    CAS  PubMed  Google Scholar 

  • Bayes A, Grant SG (2009) Neuroproteomics: understanding the molecular organization and complexity of the brain. Nat Rev Neurosci 10:635–646

    CAS  PubMed  Google Scholar 

  • Bayes A, van de Lagemaat LN, Collins MO, Croning MD, Whittle IR, Choudhary JS, Grant SG (2011) Characterization of the proteome, diseases and evolution of the human postsynaptic density. Nat Neurosci 14:19–21

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bayes A, Collins MO, Croning MD, van de Lagemaat LN, Choudhary JS, Grant SG (2012) Comparative study of human and mouse postsynaptic proteomes finds high compositional conservation and abundance differences for key synaptic proteins. PLoS ONE 7:e46683

    CAS  PubMed Central  PubMed  Google Scholar 

  • Biederer T, Sara Y, Mozhayeva M, Atasoy D, Liu X, Kavalali ET, Sudhof TC (2002) SynCAM, a synaptic adhesion molecule that drives synapse assembly. Science 297:1525–1531

    CAS  PubMed  Google Scholar 

  • Biesemann C, Gronborg M, Luquet E et al (2014) Proteomic screening of glutamatergic mouse brain synaptosomes isolated by fluorescence activated sorting. EMBO J 33:157–170

    CAS  PubMed  Google Scholar 

  • Billups B, Forsythe ID (2002) Presynaptic mitochondrial calcium sequestration influences transmission at mammalian central synapses. J Neurosci 22:5840–5847

    CAS  PubMed  Google Scholar 

  • Booth RF, Clark JB (1978) A rapid method for the preparation of relatively pure metabolically competent synaptosomes from rat brain. Biochem J 176:365–370

    CAS  PubMed Central  PubMed  Google Scholar 

  • Boyken J, Gronborg M, Riedel D, Urlaub H, Jahn R, Chua JJ (2013) Molecular profiling of synaptic vesicle docking sites reveals novel proteins but few differences between glutamatergic and GABAergic synapses. Neuron 78:285–297

    CAS  PubMed  Google Scholar 

  • Bresler T, Shapira M, Boeckers T, Dresbach T, Futter M, Garner CC, Rosenblum K, Gundelfinger ED, Ziv NE (2004) Postsynaptic density assembly is fundamentally different from presynaptic active zone assembly. J Neurosci 24:1507–1520

    CAS  PubMed  Google Scholar 

  • Burre J, Volknandt W (2007) The synaptic vesicle proteome. J Neurochem 101:1448–1462

    CAS  PubMed  Google Scholar 

  • Burre J, Beckhaus T, Schagger H, Corvey C, Hofmann S, Karas M, Zimmermann H, Volknandt W (2006) Analysis of the synaptic vesicle proteome using three gel-based protein separation techniques. Proteomics 6:6250–6262

    CAS  PubMed  Google Scholar 

  • Cajal SR (1888) Sobre las fibras nerviosas de la capa molecular del cerebelo. Rev Trim Histol Norm Patol 1:33–49

    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

    CAS  PubMed  Google Scholar 

  • Cingolani LA, Goda Y (2008) Actin in action: the interplay between the actin cytoskeleton and synaptic efficacy. Nat Rev Neurosci 9:344–356

    CAS  PubMed  Google Scholar 

  • Clarke GL, Chen J, Nishimune H (2012) Presynaptic active zone density during development and synaptic plasticity. Front Mol Neurosci 5:12

    PubMed Central  PubMed  Google Scholar 

  • Clift-O’Grady L, Desnos C, Lichtenstein Y, Faundez V, Horng JT, Kelly RB (1998) Reconstitution of synaptic vesicle biogenesis from PC12 cell membranes. Methods 16:150–159

    PubMed  Google Scholar 

  • Collins MO, Yu L, Husi H, Blackstock WP, Choudhary JS, Grant SG (2005) Robust enrichment of phosphorylated species in complex mixtures by sequential protein and peptide metal-affinity chromatography and analysis by tandem mass spectrometry. Sci Signal Transduct Knowl Environ 2005:pl6

    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 97(Suppl 1):16–23

    CAS  PubMed  Google Scholar 

  • Corti C, Aldegheri L, Somogyi P, Ferraguti F (2002) Distribution and synaptic localisation of the metabotropic glutamate receptor 4 (mGluR4) in the rodent CNS. Neuroscience 110:403–420

    CAS  PubMed  Google Scholar 

  • Cotman CW, Banker G, Churchill L, Taylor D (1974) Isolation of postsynaptic densities from rat brain. J Cell Biol 63:441–455

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cottrell BA, Galvan V, Banwait S et al (2005) A pilot proteomic study of amyloid precursor interactors in Alzheimer’s disease. Ann Neurol 58:277–289

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dalva MB, Takasu MA, Lin MZ, Shamah SM, Hu L, Gale NW, Greenberg ME (2000) EphB receptors interact with NMDA receptors and regulate excitatory synapse formation. Cell 103:945–956

    CAS  PubMed  Google Scholar 

  • Dalva MB, McClelland AC, Kayser MS (2007) Cell adhesion molecules: signalling functions at the synapse. Nat Rev Neurosci 8:206–220

    CAS  PubMed  Google Scholar 

  • De Robertis E, Rodriguez De Lores Arnaiz G, Pellegrino De Iraldi A (1962) Isolation of synaptic vesicles from nerve endings of the rat brain. Nature 194:794–795

    Google Scholar 

  • DeNardo LA, de Wit J, Otto-Hitt S, Ghosh A (2012) NGL-2 regulates input-specific synapse development in CA1 pyramidal neurons. Neuron 76:762–775

    CAS  PubMed  Google Scholar 

  • Dent EW, Kalil K (2001) Axon branching requires interactions between dynamic microtubules and actin filaments. J Neurosci 21:9757–9769

    CAS  PubMed  Google Scholar 

  • Desfrere L, Karlsson M, Hiyoshi H et al (2009) Na,K-ATPase signal transduction triggers CREB activation and dendritic growth. Proc Natl Acad Sci USA 106:2212–2217

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dosemeci A, Makusky AJ, Jankowska-Stephens E, Yang X, Slotta DJ, Markey SP (2007) Composition of the synaptic PSD-95 complex. Mol Cell Proteomics 6:1749–1760

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dunkley PR, Jarvie PE, Robinson PJ (2008) A rapid Percoll gradient procedure for preparation of synaptosomes. Nat Protoc 3:1718–1728

    CAS  PubMed  Google Scholar 

  • Elinder F, Akanda N, Tofighi R, Shimizu S, Tsujimoto Y, Orrenius S, Ceccatelli S (2005) Opening of plasma membrane voltage-dependent anion channels (VDAC) precedes caspase activation in neuronal apoptosis induced by toxic stimuli. Cell Death Differ 12:1134–1140

    CAS  PubMed  Google Scholar 

  • Fabian-Fine R, Volknandt W, Fine A, Stewart MG (2000) Age-dependent pre- and postsynaptic distribution of AMPA receptors at synapses in CA3 stratum radiatum of hippocampal slice cultures compared with intact brain. Eur J Neurosci 12:3687–3700

    CAS  PubMed  Google Scholar 

  • Falk J, Bonnon C, Girault JA, Faivre-Sarrailh C (2002) F3/contactin, a neuronal cell adhesion molecule implicated in axogenesis and myelination. Biol Cell Auspices Eur Cell Biol Organ 94:327–334

    CAS  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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ferraguti F, Klausberger T, Cobden P et al (2005) Metabotropic glutamate receptor 8-expressing nerve terminals target subsets of GABAergic neurons in the hippocampus. J Neurosci 25:10520–10536

    CAS  PubMed  Google Scholar 

  • Filiou MD, Bisle B, Reckow S, Teplytska L, Maccarrone G, Turck CW (2010) Profiling of mouse synaptosome proteome and phosphoproteome by IEF. Electrophoresis 31:1294–1301

    CAS  PubMed  Google Scholar 

  • Fogel AI, Akins MR, Krupp AJ, Stagi M, Stein V, Biederer T (2007) SynCAMs organize synapses through heterophilic adhesion. J Neurosci 27:12516–12530

    CAS  PubMed  Google Scholar 

  • Foster M, assisted by Sherrington CS (1897) A textbook of physiology part three: the central nervous system, 7th edn. MacMillan, London

  • Garner CC, Kindler S, Gundelfinger ED (2000) Molecular determinants of presynaptic active zones. Curr Opin Neurobiol 10:321–327

    CAS  PubMed  Google Scholar 

  • Glenner GG, Wong CW (1984) Alzheimer’s disease and Down’s syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun 122:1131–1135

    CAS  PubMed  Google Scholar 

  • Gray EG (1959) Electron microscopy of synaptic contacts on dendrite spines of the cerebral cortex. Nature 183:1592–1593

    CAS  PubMed  Google Scholar 

  • Gray EG, Whittaker VP (1962) The isolation of nerve endings from brain: an electron-microscopic study of cell fragments derived by homogenization and centrifugation. J Anat 96:79–88

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gronborg M, Pavlos NJ, Brunk I, Chua JJ, Munster-Wandowski A, Riedel D, Ahnert-Hilger G, Urlaub H, Jahn R (2010) Quantitative comparison of glutamatergic and GABAergic synaptic vesicles unveils selectivity for few proteins including MAL2, a novel synaptic vesicle protein. J Neurosci 30:2–12

    CAS  PubMed  Google Scholar 

  • Guenette S, Chang Y, Hiesberger T, Richardson JA, Eckman CB, Eckman EA, Hammer RE, Herz J (2006) Essential roles for the FE65 amyloid precursor protein-interacting proteins in brain development. EMBO J 25:420–431

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gundelfinger ED, Kessels MM, Qualmann B (2003) Temporal and spatial coordination of exocytosis and endocytosis. Nat Rev Mol Cell Biol 4:127–139

    CAS  PubMed  Google Scholar 

  • Guo Q, Li H, Gaddam SS, Justice NJ, Robertson CS, Zheng H (2012) Amyloid precursor protein revisited: neuron-specific expression and highly stable nature of soluble derivatives. J Biol Chem 287:2437–2445

    CAS  PubMed Central  PubMed  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

    CAS  PubMed  Google Scholar 

  • Huttner WB, Schiebler W, Greengard P, De Camilli P (1983) Synapsin I (protein I), a nerve terminal-specific phosphoprotein. III. Its association with synaptic vesicles studied in a highly purified synaptic vesicle preparation. J Cell Biol 96:1374–1388

    CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Jordan BA, Fernholz BD, Boussac M, Xu C, Grigorean G, Ziff EB, Neubert TA (2004) Identification and verification of novel rodent postsynaptic density proteins. Mol Cell Proteomics 3:857–871

    CAS  PubMed  Google Scholar 

  • Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Muller-Hill B (1987) The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 325:733–736

    CAS  PubMed  Google Scholar 

  • Kim S, Burette A, Chung HS et al (2006) NGL family PSD-95-interacting adhesion molecules regulate excitatory synapse formation. Nat Neurosci 9:1294–1301

    CAS  PubMed  Google Scholar 

  • Kins S, Lauther N, Szodorai A, Beyreuther K (2006) Subcellular trafficking of the amyloid precursor protein gene family and its pathogenic role in Alzheimer’s disease. Neurodegener Dis 3:218–226

    CAS  PubMed  Google Scholar 

  • Ko J, Kim S, Chung HS, Kim K, Han K, Kim H, Jun H, Kaang BK, Kim E (2006) SALM synaptic cell adhesion-like molecules regulate the differentiation of excitatory synapses. Neuron 50:233–245

    CAS  PubMed  Google Scholar 

  • Kogo N, Dalezios Y, Capogna M, Ferraguti F, Shigemoto R, Somogyi P (2004) Depression of GABAergic input to identified hippocampal neurons by group III metabotropic glutamate receptors in the rat. Eur J Neurosci 19:2727–2740

    PubMed  Google Scholar 

  • Kohli BM, Pflieger D, Mueller LN, Carbonetti G, Aebersold R, Nitsch RM, Konietzko U (2012) Interactome of the amyloid precursor protein APP in brain reveals a protein network involved in synaptic vesicle turnover and a close association with Synaptotagmin-1. J Proteome Res 11:4075–4090

    CAS  PubMed  Google Scholar 

  • Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W (2004) Reversal of obesity by targeted ablation of adipose tissue. Nat Med 10:625–632

    CAS  PubMed  Google Scholar 

  • Korshunova I, Caroni P, Kolkova K, Berezin V, Bock E, Walmod PS (2008) Characterization of BASP1-mediated neurite outgrowth. J Neurosci Res 86:2201–2213

    CAS  PubMed  Google Scholar 

  • Koticha D, Babiarz J, Kane-Goldsmith N, Jacob J, Raju K, Grumet M (2005) Cell adhesion and neurite outgrowth are promoted by neurofascin NF155 and inhibited by NF186. Mol Cell Neurosci 30:137–148

    CAS  PubMed  Google Scholar 

  • Lassek M, Weingarten J, Einsfelder U, Brendel P, Muller U, Volknandt W (2013) Amyloid precursor proteins are constituents of the presynaptic active zone. J Neurochem 127:48–56

    CAS  PubMed  Google Scholar 

  • Lazarov O, Morfini GA, Lee EB et al (2005) Axonal transport, amyloid precursor protein, kinesin-1, and the processing apparatus: revisited. J Neurosci 25:2386–2395

    CAS  PubMed  Google Scholar 

  • Levy M, Faas GC, Saggau P, Craigen WJ, Sweatt JD (2003) Mitochondrial regulation of synaptic plasticity in the hippocampus. J Biol Chem 278:17727–17734

    CAS  PubMed  Google Scholar 

  • Li KW, Hornshaw MP, Van Der Schors RC et al (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

    CAS  PubMed  Google Scholar 

  • Li K, Hornshaw MP, van Minnen J, 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

    CAS  PubMed  Google Scholar 

  • Lorent K, Overbergh L, Moechars D, De Strooper B, Van Leuven F, Van den Berghe H (1995) Expression in mouse embryos and in adult mouse brain of three members of the amyloid precursor protein family, of the alpha-2-macroglobulin receptor/low density lipoprotein receptor-related protein and of its ligands apolipoprotein E, lipoprotein lipase, alpha-2-macroglobulin and the 40,000 molecular weight receptor-associated protein. Neuroscience 65:1009–1025

    CAS  PubMed  Google Scholar 

  • Lyckman AW, Confaloni AM, Thinakaran G, Sisodia SS, Moya KL (1998) Post-translational processing and turnover kinetics of presynaptically targeted amyloid precursor superfamily proteins in the central nervous system. J Biol Chem 273:11100–11106

    CAS  PubMed  Google Scholar 

  • Maas C, Torres VI, Altrock WD et al (2012) Formation of Golgi-derived active zone precursor vesicles. J Neurosci 32:11095–11108

    CAS  PubMed Central  PubMed  Google Scholar 

  • Marin R, Ramirez CM, Gonzalez M, Gonzalez-Munoz E, Zorzano A, Camps M, Alonso R, Diaz M (2007) Voltage-dependent anion channel (VDAC) participates in amyloid beta-induced toxicity and interacts with plasma membrane estrogen receptor alpha in septal and hippocampal neurons. Mol Membr Biol 24:148–160

    CAS  PubMed  Google Scholar 

  • Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci USA 82:4245–4249

    CAS  PubMed Central  PubMed  Google Scholar 

  • Missler M, Sudhof TC, Biederer T (2012) Synaptic cell adhesion. Cold Spring Harb Perspect Biol 4:a005694

    PubMed Central  PubMed  Google Scholar 

  • Mohammadi K, Kometiani P, Xie Z, Askari A (2001) Role of protein kinase C in the signal pathways that link Na+/K + -ATPase to ERK1/2. J Biol Chem 276:42050–42056

    CAS  PubMed  Google Scholar 

  • Morciano M, Burre J, Corvey C, Karas M, Zimmermann H, Volknandt W (2005) Immunoisolation of two synaptic vesicle pools from synaptosomes: a proteomics analysis. J Neurochem 95:1732–1745

    CAS  PubMed  Google Scholar 

  • Morciano M, Beckhaus T, Karas M, Zimmermann H, Volknandt W (2009) The proteome of the presynaptic active zone: from docked synaptic vesicles to adhesion molecules and maxi-channels. J Neurochem 108:662–675

    CAS  PubMed  Google Scholar 

  • Nagy A, Baker RR, Morris SJ, Whittaker VP (1976) The preparation and characterization of synaptic vesicles of high purity. Brain Res 109:285–309

    CAS  PubMed  Google Scholar 

  • Nelson JC, Stavoe AK, Colon-Ramos DA (2013) The actin cytoskeleton in presynaptic assembly. Cell Adhes Migr 7

  • Nensa FM, Neumann MH, Schrotter A et al (2014) Amyloid beta A4 precursor protein-binding family B member 1 (FE65) interactomics revealed synaptic vesicle glycoprotein 2A (SV2A) and sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) as new binding proteins in the human brain. Mol Cell Proteomics 13:475–488

    CAS  PubMed  Google Scholar 

  • Norstrom EM, Zhang C, Tanzi R, Sisodia SS (2010) Identification of NEEP21 as a ss-amyloid precursor protein-interacting protein in vivo that modulates amyloidogenic processing in vitro. J Neurosci 30:15677–15685

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nyiri G, Cserep C, Szabadits E, Mackie K, Freund TF (2005) CB1 cannabinoid receptors are enriched in the perisynaptic annulus and on preterminal segments of hippocampal GABAergic axons. Neuroscience 136:811–822

    CAS  PubMed  Google Scholar 

  • Ohtsuka T (2013) CAST: functional scaffold for the integrity of the presynaptic active zone. Neurosci Res 76:10–15

    CAS  PubMed  Google Scholar 

  • Okabe S (2007) Molecular anatomy of the postsynaptic density. Mol Cell Neurosci 34:503–518

    CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Perkins GA, Tjong J, Brown JM, Poquiz PH, Scott RT, Kolson DR, Ellisman MH, Spirou GA (2010) The micro-architecture of mitochondria at active zones: electron tomography reveals novel anchoring scaffolds and cristae structured for high-rate metabolism. J Neurosci 30:1015–1026

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pfenninger K, Sandri C, Akert K, Eugster CH (1969) Contribution to the problem of structural organization of the presynaptic area. Brain Res 12:10–18

    CAS  PubMed  Google Scholar 

  • Phillips GR, Huang JK, Wang Y et al (2001) The presynaptic particle web: ultrastructure, composition, dissolution, and reconstitution. Neuron 32:63–77

    CAS  PubMed  Google Scholar 

  • Pitsch J, Opitz T, Borm V, Woitecki A, Staniek M, Beck H, Becker AJ, Schoch S (2012) The presynaptic active zone protein RIM1alpha controls epileptogenesis following status epilepticus. J Neurosci 32:12384–12395

    CAS  PubMed  Google Scholar 

  • Pocklington AJ, Cumiskey M, Armstrong JD, Grant SG (2006) The proteomes of neurotransmitter receptor complexes form modular networks with distributed functionality underlying plasticity and behaviour. Mol Syst Biol 2(2006):0023

    PubMed  Google Scholar 

  • Ramos-Ortolaza DL, Bushlin I, Abul-Husn N, Annangudi SP, Sweedler J, Devi LA (2010) Quantitative neuroproteomics of the synapse. Methods Mol Biol 615:227–246

    CAS  PubMed Central  PubMed  Google Scholar 

  • Reinhard C, Hebert SS, De Strooper B (2005) The amyloid-beta precursor protein: integrating structure with biological function. EMBO J 24:3996–4006

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rietschel B, Arrey TN, Meyer B, Bornemann S, Schuerken M, Karas M, Poetsch A (2009a) Elastase digests: new ammunition for shotgun membrane proteomics. Mol Cell Proteomics 8:1029–1043

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rietschel B, Bornemann S, Arrey TN, Baeumlisberger D, Karas M, Meyer B (2009b) Membrane protein analysis using an improved peptic in-solution digestion protocol. Proteomics 9:5553–5557

    CAS  PubMed  Google Scholar 

  • Ring S, Weyer SW, Kilian SB et al (2007) The secreted beta-amyloid precursor protein ectodomain APPs alpha is sufficient to rescue the anatomical, behavioral, and electrophysiological abnormalities of APP-deficient mice. J Neurosci 27:7817–7826

    CAS  PubMed  Google Scholar 

  • Rossner S, Fuchsbrunner K, Lange-Dohna C, Hartlage-Rubsamen M, Bigl V, Betz A, Reim K, Brose N (2004) Munc13-1-mediated vesicle priming contributes to secretory amyloid precursor protein processing. J Biol Chem 279:27841–27844

    CAS  PubMed  Google Scholar 

  • Rowland KC, Irby NK, Spirou GA (2000) Specialized synapse-associated structures within the calyx of Held. J Neurosci 20:9135–9144

    CAS  PubMed  Google Scholar 

  • Sandbrink R, Masters CL, Beyreuther K (1994) APP gene family: unique age-associated changes in splicing of Alzheimer’s betaA4-amyloid protein precursor. Neurobiol Dis 1:13–24

    CAS  PubMed  Google Scholar 

  • Schmitz D, Mellor J, Frerking M, Nicoll RA (2001) Presynaptic kainate receptors at hippocampal mossy fiber synapses. Proc Natl Acad Sci USA 98:11003–11008

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schoch S, Gundelfinger ED (2006) Molecular organization of the presynaptic active zone. Cell Tissue Res 326:379–391

    CAS  PubMed  Google Scholar 

  • Schrenk-Siemens K, Perez-Alcala S, Richter J, Lacroix E, Rahuel J, Korte M, Muller U, Barde YA, Bibel M (2008) Embryonic stem cell-derived neurons as a cellular system to study gene function: lack of amyloid precursor proteins APP and APLP2 leads to defective synaptic transmission. Stem Cells 26:2153–2163

    CAS  PubMed  Google Scholar 

  • Schrimpf SP, Meskenaite V, Brunner E, Rutishauser D, Walther P, Eng J, Aebersold R, Sonderegger P (2005) Proteomic analysis of synaptosomes using isotope-coded affinity tags and mass spectrometry. Proteomics 5:2531–2541

    CAS  PubMed  Google Scholar 

  • Shigemoto R, Kulik A, Roberts JD, Ohishi H, Nusser Z, Kaneko T, Somogyi P (1996) Target-cell-specific concentration of a metabotropic glutamate receptor in the presynaptic active zone. Nature 381:523–525

    CAS  PubMed  Google Scholar 

  • Sihra TS, Rodriguez-Moreno A (2013) Presynaptic kainate receptor-mediated bidirectional modulatory actions: mechanisms. Neurochem Int 62:982–987

    CAS  PubMed  Google Scholar 

  • Slunt HH, Thinakaran G, Von Koch C, Lo AC, Tanzi RE, Sisodia SS (1994) Expression of a ubiquitous, cross-reactive homologue of the mouse beta-amyloid precursor protein (APP). J Biol Chem 269:2637–2644

    CAS  PubMed  Google Scholar 

  • Soba P, Eggert S, Wagner K et al (2005) Homo- and heterodimerization of APP family members promotes intercellular adhesion. EMBO J 24:3624–3634

    CAS  PubMed Central  PubMed  Google Scholar 

  • Soltys BJ, Gupta RS (1999) Mitochondrial-matrix proteins at unexpected locations: are they exported? Trends Biochem Sci 24:174–177

    CAS  PubMed  Google Scholar 

  • Sperlagh B, Heinrich A, Csolle C (2007) P2 receptor-mediated modulation of neurotransmitter release-an update. Purinergic Signal 3:269–284

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sudhof TC (2012) The presynaptic active zone. Neuron 75:11–25

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sudhof TC, Rizo J (2011) Synaptic vesicle exocytosis. Cold Spring Harb Perspect Biol 3

  • Suzuki T, Okumura-Noji K, Tanaka R, Tada T (1994) Rapid translocation of cytosolic Ca2+/calmodulin-dependent protein kinase II into postsynaptic density after decapitation. J Neurochem 63:1529–1537

    CAS  PubMed  Google Scholar 

  • Szodorai A, Kuan YH, Hunzelmann S et al (2009) APP anterograde transport requires Rab3A GTPase activity for assembly of the transport vesicle. J Neurosci 29:14534–14544

    CAS  PubMed Central  PubMed  Google Scholar 

  • Takamori S, Holt M, Stenius K et al (2006) Molecular anatomy of a trafficking organelle. Cell 127:831–846

    CAS  PubMed  Google Scholar 

  • Tang Y, Zucker RS (1997) Mitochondrial involvement in post-tetanic potentiation of synaptic transmission. Neuron 18:483–491

    CAS  PubMed  Google Scholar 

  • Tannu NS, Hemby SE (2006) Two-dimensional fluorescence difference gel electrophoresis for comparative proteomics profiling. Nat Protoc 1:1732–1742

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tidow H, Aperia A, Nissen P (2010) How are ion pumps and agrin signaling integrated? Trends Biochem Sci 35:653–659

    CAS  PubMed  Google Scholar 

  • Tienari PJ, De Strooper B, Ikonen E et al (1996) The beta-amyloid domain is essential for axonal sorting of amyloid precursor protein. EMBO J 15:5218–5229

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tsang CW, Estey MP, DiCiccio JE, Xie H, Patterson D, Trimble WS (2011) Characterization of presynaptic septin complexes in mammalian hippocampal neurons. Biol Chem 392:739–749

    CAS  PubMed  Google Scholar 

  • van de Goor J, Ramaswami M, Kelly R (1995) Redistribution of synaptic vesicles and their proteins in temperature-sensitive shibire(ts1) mutant Drosophila. Proc Natl Acad Sci USA 92:5739–5743

    PubMed Central  PubMed  Google Scholar 

  • van Montfort BA, Canas B, Duurkens R, Godovac-Zimmermann J, Robillard GT (2002) Improved in-gel approaches to generate peptide maps of integral membrane proteins with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. J Mass Spectrom 37:322–330

    PubMed  Google Scholar 

  • Volknandt W, Karas M (2012) Proteomic analysis of the presynaptic active zone. Exp Brain Res 217:449–461

    CAS  PubMed  Google Scholar 

  • Volknandt W, Zimmermann H (1986) Acetylcholine, ATP, and proteoglycan are common to synaptic vesicles isolated from the electric organs of electric eel and electric catfish as well as from rat diaphragm. J Neurochem 47:1449–1462

    CAS  PubMed  Google Scholar 

  • Wang Z, Wang B, Yang L, Guo Q, Aithmitti N, Songyang Z, Zheng H (2009) Presynaptic and postsynaptic interaction of the amyloid precursor protein promotes peripheral and central synaptogenesis. J Neurosci 29:10788–10801

    CAS  PubMed Central  PubMed  Google Scholar 

  • Weingarten J, Lassek M, Mueller BF et al (2014) The proteome of the presynaptic active zone from mouse brain. Mol Cell Neurosci 59C:106–118

    Google Scholar 

  • Weyer SW, Klevanski M, Delekate A et al (2011) APP and APLP2 are essential at PNS and CNS synapses for transmission, spatial learning and LTP. EMBO J 30:2266–2280

    CAS  PubMed Central  PubMed  Google Scholar 

  • Whittaker VP, Michaelson IA, Kirkland RJ (1964) The separation of synaptic vesicles from nerve-ending particles (‘synaptosomes’). Biochem J 90:293–303

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wilson RI, Nicoll RA (2001) Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature 410:588–592

    CAS  PubMed  Google Scholar 

  • Wolfe MS, Guenette SY (2007) APP at a glance. J Cell Sci 120:3157–3161

    CAS  PubMed  Google Scholar 

  • Xie Z, Askari A (2002) Na(+)/K(+)-ATPase as a signal transducer. Eur J Biochem FEBS 269:2434–2439

    CAS  Google Scholar 

  • Yang F, He XP, Russell J, Lu B (2003) Ca2+ influx-independent synaptic potentiation mediated by mitochondrial Na(+)-Ca2+ exchanger and protein kinase C. J Cell Biol 163:511–523

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yang G, Gong YD, Gong K et al (2005) Reduced synaptic vesicle density and active zone size in mice lacking amyloid precursor protein (APP) and APP-like protein 2. Neurosci Lett 384:66–71

    CAS  PubMed  Google Scholar 

  • Yang L, Wang B, Long C, Wu G, Zheng H (2007) Increased asynchronous release and aberrant calcium channel activation in amyloid precursor protein deficient neuromuscular synapses. Neuroscience 149:768–778

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yao J, Nowack A, Kensel-Hammes P, Gardner RG, Bajjalieh SM (2010) Cotrafficking of SV2 and synaptotagmin at the synapse. J Neurosci 30:5569–5578

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yoshimura Y, Nomura T, Yamauchi T (1996) Purification and characterization of active fragment of Ca2+/calmodulin-dependent protein kinase II from the post-synaptic density in the rat forebrain. J Biochem 119:268–273

    CAS  PubMed  Google Scholar 

  • Yoshimura Y, Yamauchi Y, Shinkawa T, Taoka M, Donai H, Takahashi N, Isobe T, Yamauchi T (2004) Molecular constituents of the postsynaptic density fraction revealed by proteomic analysis using multidimensional liquid chromatography-tandem mass spectrometry. J Neurochem 88:759–768

    CAS  PubMed  Google Scholar 

  • Zampighi GA, Fisher RS (1997) Polyhedral protein cages encase synaptic vesicles and participate in their attachment to the active zone. J Struct Biol 119:347–359

    CAS  PubMed  Google Scholar 

  • Zhai RG, Vardinon-Friedman H, Cases-Langhoff C, Becker B, Gundelfinger ED, Ziv NE, Garner CC (2001) Assembling the presynaptic active zone: a characterization of an active one precursor vesicle. Neuron 29:131–143

    CAS  PubMed  Google Scholar 

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Acknowledgment

We thank Dr. Herbert Zimmermann for helpful comments.

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Authors and Affiliations

  1. Molecular and Cellular Neurobiology, Goethe University, Frankfurt, Germany

    Melanie Laßek, Jens Weingarten & Walter Volknandt

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  1. Melanie Laßek
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  2. Jens Weingarten
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  3. Walter Volknandt
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Correspondence to Walter Volknandt.

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Laßek, M., Weingarten, J. & Volknandt, W. The synaptic proteome. Cell Tissue Res 359, 255–265 (2015). https://doi.org/10.1007/s00441-014-1943-4

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