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Transgenic Models in Pharmacology pp 229–259Cite as

Transgenic Mouse Models in the Analysis of Neurotransmitter Release Mechanisms

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 159))

Abstract

The release of neurotransmitter molecules from synaptic vesicles is of outmost importance for the communication between cells in the nervous system. Before their fusion with the plasma membrane, vesicles undergo a multistep process which is tightly regulated by a large number of proteins. After fusion, a similarly complex protein machinery is involved in the recycling of the vesicle membrane. In addition, many proteins modulate the amount of neurotransmitter being released, accounting at least in part for the tremendous plasticity of human brain function. Here we review the current knowledge that has been gained by the targeted disruption of genes encoding presynaptic proteins in mice. In the first chapters, we discuss those proteins which have been assigned to a specific step in the synaptic vesicle cycle. In particular, we cover proteins involved in transmitter and ion transport into synaptic vesicles, in synaptic vesicle docking and priming, in Ca2+ signaling and sensing, and in the fusion process itself. Next, we discuss proteins which are not required for neurotransmitter release, but which modulate its extent and thus most likely play a role in synaptic plasticity. Finally, we review what is known about pharmacological tools which interfere with neurotransmitter release. It can be expected that the use of transgenic mouse models will continue to increase over the coming years and that this strategy will help to finally unravel the secrets of neurotransmitter release.

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References

  • Aihara Y, Mashima H, Onda H, Hisano S, Kasuya H, Hori T, Yamada S, Tomura H, Yamada Y, Inoue I, Kojima I, Takeda J (2000) Molecular cloning of a novel brain-type Na(+)-dependent inorganic phosphate cotransporter. J Neurochem 74:2622–2625

    Article  PubMed  CAS  Google Scholar 

  • Aldea M, Jun K, Shin HS, Andres-Mateos E, Solis-Garrido LM, Montiel C, Garcia AG, Albillos A (2002) A perforated patch-clamp study of calcium currents and exocytosis in chromaffin cells of wild-type and alpha(1A) knockout mice. J Neurochem 81:911–921

    Article  PubMed  CAS  Google Scholar 

  • Antonin W, Riedel D, Fischer von Mollard G (2000) The SNARE Vti1a-beta is localized to small synaptic vesicles and participates in a novel SNARE complex. J Neurosci 20:5724–5732

    PubMed  CAS  Google Scholar 

  • Augustin I, Korte S, Rickmann M, Kretzschmar HA, Südhof TC, Herms JW, Brose N (2001) The cerebellum-specific Munc13 isoform Munc13-3 regulates cerebellar synaptic transmission and motor learning in mice. J Neurosci 21:10–17

    PubMed  CAS  Google Scholar 

  • Augustin I, Rosenmund C, Südhof TC, Brose N (1999) Munc 13-1 is essential for fusion competence of glutamatergic synaptic vesicles. Nature 400:457–461

    Article  PubMed  CAS  Google Scholar 

  • Augustine GJ, Burns ME, DeBello WM, Pettit DL, Schweizer FE (1996) Exocytosis:proteins and perturbations. Annu Rev Pharmacol Toxicol 36:659–701

    Article  PubMed  CAS  Google Scholar 

  • Ayata C, Shimizu-Sasamata M, Lo EH, Noebels JL, Moskowitz MA (2000) Impaired neurotransmitter release and elevated threshold for cortical spreading depression in mice with mutations in the alpha1A subunit of P/Q type calcium channels. Neuroscience 95:639–645

    Article  PubMed  CAS  Google Scholar 

  • Betz A, Ashery U, Rickmann M, Augustin I, Neher E, Südhof TC, Rettig J, Brose N (1998) Munc13-1 is a presynaptic phorbol ester receptor that enhances neurotransmitter release. Neuron 21:123–136

    Article  PubMed  CAS  Google Scholar 

  • Betz A, Thakur P, Junge HJ, Ashery U, Rhee JS, Scheuss V, Rosenmund C, Rettig J, Brose N (2001) Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming. Neuron 30:183–196

    Article  PubMed  CAS  Google Scholar 

  • Bollmann JH, Sakmann B, Borst JG (2000) Calcium sensitivity of glutamate release in a calyx-type terminal. Science 289:953–957

    Article  PubMed  CAS  Google Scholar 

  • Brodin L, Low P, Shupliakov O (2000) Sequential steps in clathrin-mediated synaptic vesicle endocytosis. Curr Opin Neurobiol 10:312–320

    Article  PubMed  CAS  Google Scholar 

  • Brose N (1998) Synaptic vesicle proteins—a genetic approach. In: Linial M, Grasso A, Lazarovici M (eds) Cellular and molecular mechanisms of toxin action—secretory systems. Harwood, Amsterdam, p 45

    Google Scholar 

  • Brose N, Rosenmund C, Rettig J (2000) Regulation of transmitter release by Unc-13 and its homologues. Curr Opin Neurobiol 10:303–311

    Article  PubMed  CAS  Google Scholar 

  • Castillo PE, Janz R, Südhof TC, Tzounopoulos T, Malenka RC, Nicoll RA (1997) Rab3A is essential for mossy fibre long-term potentiation in the hippocampus. Nature 388:590–593

    Article  PubMed  CAS  Google Scholar 

  • Castillo PE, Schoch S, Schmitz F, Südhof TC, Malenka RC (2002) RIM1alpha is required for presynaptic long-term potentiation. Nature 415:327–330

    Article  PubMed  CAS  Google Scholar 

  • Chapman ER (2002) Synaptotagmin: A Ca2+ sensor that triggers exocytosis? Nat Rev Mol Cell Biol 3:498–508

    Article  PubMed  CAS  Google Scholar 

  • Chen X, Tomchick DR, Kovrigin E, Arac D, Machius M, Südhof TC, Rizo J (2002) Threedimensional structure of the complexin/SNARE complex. Neuron 33:397–409

    Article  PubMed  CAS  Google Scholar 

  • Chin LS, Li L, Ferreira A, Kosik KS, Greengard P (1995) Impairment of axonal development and of synaptogenesis in hippocampal neurons of synapsin I-deficient mice. Proc Natl Acad Sci USA 92:9230–9234

    Article  PubMed  CAS  Google Scholar 

  • Cole TB, Wenzel HJ, Kafer KE, Schwartzkroin PA, Palmiter RD (1999) Elimination of zinc from synaptic vesicles in the intact mouse brain by disruption of the ZnT3 gene. Proc Natl Acad Sci USA 96:1716–1721

    Article  PubMed  CAS  Google Scholar 

  • Cremona O, De Camilli P (1997) Synaptic vesicle endocytosis. Curr Opin Neurobiol 7:323–330

    Article  PubMed  CAS  Google Scholar 

  • Cremona O, Di Paolo G, Wenk MR, Luthi A, Kim WT, Takei K, Daniell L, Nemoto Y, Shears SB, Flavell RA, McCormick DA, De Camilli P (1999) Essential role of phosphoinositide metabolism in synaptic vesicle recycling. Cell 99:179–188

    Article  PubMed  CAS  Google Scholar 

  • Crowder KM, Gunther JM, Jones TA, Hale BD, Zhang HZ, Peterson MR, Scheller RH, Chavkin C, Bajjalieh SM (1999) Abnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A). Proc Natl Acad Sci USA 96:15268–15273

    Article  PubMed  CAS  Google Scholar 

  • Di Paolo G, Sankaranarayanan S, Wenk MR, Daniell L, Perucco E, Caldarone BJ, Flavell R, Picciotto MR, Ryan TA, Cremona O, De Camilli P (2002) Decreased synaptic vesicle recycling efficiency and cognitive deficits in amphiphysin 1 knockout mice. Neuron 33:789–804

    Article  PubMed  Google Scholar 

  • Dulubova I, Sugita S, Hill S, Hosaka M, Fernandez I, Südhof TC, Rizo J (1999) A conformational switch in syntaxin during exocytosis: role of munc18. EMBO J 18:4372–4382

    Article  PubMed  CAS  Google Scholar 

  • Eiden LE (2000) The vesicular neurotransmitter transporters: current perspectives and future prospects. FASEB J 14:2396–2400

    Article  PubMed  CAS  Google Scholar 

  • Erickson JD, Eiden LE, Hoffman BJ (1992) Expression cloning of a reserpine-sensitive vesicular monoamine transporter. Proc Natl Acad Sci USA 89:10993–10997

    Article  PubMed  CAS  Google Scholar 

  • Eshkind LG, and Leube RE (1995) Mice lacking synaptophysin reproduce and form typical synaptic vesicles. Cell Tissue Res 282:423–433

    Article  PubMed  CAS  Google Scholar 

  • Feng J, Chi P, Blanpied TA, Xu Y, Magarinos AM, Ferreira A, Takahashi RH, Kao HT, McEwen BS, Ryan TA, Augustine GJ, Greengard P (2002) Regulation of neurotransmitter release by synapsin III. J Neurosci 22:4372–4380

    PubMed  CAS  Google Scholar 

  • Ferguson GD, Anagnostaras SG, Silva AJ, Herschman HR (2000) Deficits in memory and motor performance in synaptotagmin IV mutant mice. Proc Natl Acad Sci USA 97:5598–5603

    Article  PubMed  CAS  Google Scholar 

  • Fernandez-Chacon R, Alvarez de Toledo G, Hammer RE, Südhof TC (1999) Analysis of SCAMP1 function in secretory vesicle exocytosis by means of gene targeting in mice. J Biol Chem 274:32551–32554

    Article  PubMed  CAS  Google Scholar 

  • Fernandez-Chacon R, Konigstorfer A, Gerber SH, Garcia J, Matos MF, Stevens CF, Brose N, Rizo J, Rosenmund C, Südhof TC (2001) Synaptotagmin I functions as a calcium regulator of release probability. Nature 410:41–49

    Article  PubMed  CAS  Google Scholar 

  • Fernandez-Chacon R, Shin O-H, Konigstorfer A, Matos M, Meyer A, Garcia J, Gerber SH, Rizo J, Südhof TC, Rosenmund C (2002) Structure/function analysis of Ca2+ binding to the C2A-domain of Synaptotagmin 1. J Neurosci, in press

    Google Scholar 

  • Fernandez-Chacon R, Südhof TC (1999) Genetics of synaptic vesicle function: toward the complete functional anatomy of an organelle. Annu Rev Physiol 61:753–776

    Article  PubMed  CAS  Google Scholar 

  • Ferreira A, Han H, Greengard P, Kosik KS (1995) Suppression of Synapsin II inhibits the formation and maintenance of synapses in hippocampal culture. Proc Natl Acad Sci USA 92:9225–9229

    Article  PubMed  CAS  Google Scholar 

  • Ferreira A, Rapoport M (2002) The synapsins: beyond the regulation of neurotransmitter release. Cell Mol Life Sci 59:589–595

    Article  PubMed  CAS  Google Scholar 

  • Fischer von Mollard G, Stahl B, Walch-Solimena C, Takei K, Daniels L, Khoklatchev A, De Camilli P, Südhof TC, Jahn R (1994) Localization of Rab5 to synaptic vesicles identifies endosomal intermediate in synaptic vesicle recycling pathway. Eur J Cell Biol 65:319–326

    PubMed  CAS  Google Scholar 

  • Fletcher CF, Lutz CM, O’Sullivan TN, Shaughnessy JD Jr, Hawkes R, Frankel WN, Copeland NG, Jenkins NA (1996) Absence epilepsy in tottering mutant mice is associated with calcium channel defects. Cell 87:607–617

    Article  PubMed  CAS  Google Scholar 

  • Fon EA, Pothos EN, Sun BC, Killeen N, Sulzer D, Edwards RH (1997) Vesicular transport regulates monoamine storage and release but is not essential for amphetamine action. Neuron 19:1271–1283

    Article  PubMed  CAS  Google Scholar 

  • Fumagalli F, Gainetdinov RR, Wang YM, Valenzano KJ, Miller GW, Caron MG (1999) Increased methamphetamine neurotoxicity in heterozygous vesicular monoamine transporter 2 knockout mice. J Neurosci 19:2424–2431

    PubMed  CAS  Google Scholar 

  • Gad H, Löw P, Zotova E, Brodin L, Shupliakov O (1998) Dissociation between Ca2+-evoked synaptic vesicle exocytosis and clathrin-mediated endocytosis at a central vertebrate synapse. Neuron 21:607–616

    Article  PubMed  CAS  Google Scholar 

  • Garner CC, Zhai RG, Gundelfinger ED, Ziv NE (2002) Molecular mechanisms of CNS synaptogenesis. Trends Neurosci 25:251–258

    Article  CAS  Google Scholar 

  • Geppert M, Bolshakov VY, Siegelbaum SA, Takei K, De Camilli P, Hammer RE, Südhof TC (1994a) The role of Rab3A in neurotransmitter release. Nature 369:493–497

    Article  PubMed  CAS  Google Scholar 

  • Geppert M, Goda Y, Hammer RE, Li C, Rosahl TW, Stevens CF, Südhof TC (1994b) Synaptotagmin I: a major Ca2+ sensor for transmitter release at a central synapse. Cell 79:717–727

    Article  PubMed  CAS  Google Scholar 

  • Geppert M, Goda Y, Stevens CF, Südhof TC (1997) The small GTP-binding protein Rab3A regulates a late step in synaptic vesicle fusion. Nature 387:810–814

    Article  PubMed  CAS  Google Scholar 

  • Geppert M, Khvotchev M, Krasnoperov V, Goda Y, Missler M, Hammer RE, Ichtchenko K, Petrenko AG, Südhof TC (1998) Neurexin I alpha is a major alpha-latrotoxin receptor that cooperates in alpha-latrotoxin action. J Biol Chem 273:1705–1710

    Article  PubMed  CAS  Google Scholar 

  • Gras C, Herzog E, Bellenchi GC, Bernard V, Ravassard P, Pohl M, Gasnier B, Giros B, El Mestikawy S (2002) A third vesicular glutamate transporter expressed by cholinergic and serotoninergic neurons. J Neurosci 22:5442–5451

    PubMed  CAS  Google Scholar 

  • Harlow ML, Ress D, Stoschek A, Marshall RM, McMahan UJ (2001) The architecture of active zone material at the frog’s neuromuscular junction. Nature 409:479–484

    Article  PubMed  CAS  Google Scholar 

  • Hatakeyama S, Wakamori M, Ino M, Miyamoto N, Takahashi E, Yoshinaga T, Sawada K, Imoto K, Tanaka I, Yoshizawa T, Nishizawa Y, Mori Y, Niidome T, Shoji S (2001) Differential nociceptive responses in mice lacking the alpha(1B) subunit of N-type Ca2+ channels. Neuroreport 12:2423–2427

    Article  PubMed  CAS  Google Scholar 

  • Haucke V, De Camilli P (1999) AP-2 recruitment to synaptotagmin stimulated by tyrosine-based endocytic motifs. Science 285:1268–1271

    Article  PubMed  CAS  Google Scholar 

  • Heuser JE, Reese TS (1973) Evidence for recycling of synaptic vesicle membrane during transmitter release at the frog neuromuscular junction. J Cell Biol 57:315–344

    Article  PubMed  CAS  Google Scholar 

  • Heuser JE, Reese TS, Landis DM (1974) Functional changes in frog neuromuscular junctions studied with freeze-fracture. J Neurocytol 3:109–131

    Article  PubMed  CAS  Google Scholar 

  • Hilfiker S, Pieribone VA, Czernik AJ, Kao HT, Augustine GJ, Greengard P (1999) Synapsins as regulators of neurotransmitter release. Philos Trans R Soc Lond B Biol Sci 354:269–279

    Article  PubMed  CAS  Google Scholar 

  • Huang L, Gitschier J (1997) A novel gene involved in zinc transport is deficient in the lethal milk mouse. Nat Genet 17:292–297

    Article  PubMed  CAS  Google Scholar 

  • Ino M, Yoshinaga T, Wakamori M, Miyamoto N, Takahashi E, Sonoda J, Kagaya T, Oki T, Nagasu T, Nishizawa Y, Tanaka I, Imoto K, Aizawa S, Koch S, Schwartz A, Niidome T, Sawada K, Mori Y (2001) Functional disorders of the sympathetic nervous system in mice lacking the alpha 1B subunit (Cav 2.2) of N-type calcium channels. Proc Natl Acad Sci USA 98:5323–5328

    Article  PubMed  CAS  Google Scholar 

  • Ishizaki H, Miyoshi J, Kamiya H, Togawa A, Tanaka M, Sasaki T, Endo K, Mizoguchi A, Ozawa S, and Takai Y (2000) Role of rab GDP dissociation inhibitor alpha in regulating plasticity of hippocampal neurotransmission. Proc Natl Acad Sci USA 97:11587–11592

    Article  PubMed  CAS  Google Scholar 

  • Itokawa K, Sora I, Schindler CW, Itokawa M, Takahashi N, Uhl GR (1999) Heterozygous VMAT2 knockout mice display prolonged QT intervals: possible contributions to sudden death. Brain Res Mol Brain Res 71:354–357

    Article  PubMed  CAS  Google Scholar 

  • Iversen L (2000) Neurotransmitter transporters: fruitful targets for CNS drug discovery. Mol Psychiatry 5:357–362

    Article  PubMed  CAS  Google Scholar 

  • Jahn R, Südhof TC (1999) Membrane fusion and exocytosis. Annu Rev Biochem 68:863–911

    Article  PubMed  CAS  Google Scholar 

  • Janz R, Südhof TC, Hammer RE, Unni V, Siegelbaum SA, Bolshakov VY (1999a) Essential roles in synaptic plasticity for synaptogyrin I and synaptophysin I. Neuron 24:687–700

    Article  PubMed  CAS  Google Scholar 

  • Janz R, Goda Y, Geppert M, Missler M, Südhof TC (1999b) SV2A and SV2B function as redundant Ca2+ regulators in neurotransmitter release. Neuron 24:1003–1016

    Article  PubMed  CAS  Google Scholar 

  • Jorgensen EM, Hartwieg E, Schuske K, Nonet ML, Jin Y, Horvitz HR (1995) Defective recycling of synaptic vesicles in synaptotagmin mutants of Caenorhabditis elegans. Nature 378:196–199

    Article  PubMed  CAS  Google Scholar 

  • Jun K, Piedras-Renteria ES, Smith SM, Wheeler DB, Lee SB, Lee TG, Chin H, Adams ME, Scheller RH, Tsien RW, Shin HS (1999) Ablation of P/Q-type Ca2+ channel currents, altered synaptic transmission, and progressive ataxia in mice lacking the alpha(1A)-subunit. Proc Natl Acad Sci USA 96:15245–15250

    Article  PubMed  CAS  Google Scholar 

  • Kim C, Jun K, Lee T, Kim SS, McEnery MW, Chin H, Kim HL, Park JM, Kim DK, Jung SJ, Kim J, Shin HS (2001) Altered nociceptive response in mice deficient in the alpha(1B) subunit of the voltage-dependent calcium channel. Mol Cell Neurosci 18:235–245

    Article  PubMed  CAS  Google Scholar 

  • Koushika SP, Richmond JE, Hadwiger G, Weimer RM, Jorgensen EM, Nonet ML (2001) A post-docking role for active zone protein Rim. Nat Neurosci 4:997–1005

    Article  PubMed  CAS  Google Scholar 

  • Leenders AG, Lopes da Silva FH, Ghijsen WE, Verhage M (2001) Rab3a is involved in transport of synaptic vesicles to the active zone in mouse brain nerve terminals. Mol Biol Cell 12:3095–3102

    PubMed  CAS  Google Scholar 

  • Li L, Chin LS, Shupliakov O, Brodin L, Sihra TS, Hvalby O, Jensen V, Zheng D, McNamara JO, Greengard P, Andersen P (1995) Impairment of synaptic vesicle clustering and of synaptic transmission, and increased seizure propensity, in synapsin I-deficient mice. Proc Natl Acad Sci USA 92:9235–9239

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Edwards RH (1997) The role of vesicular transport proteins in synaptic transmission and neural degeneration. Annu Rev Neurosci 20:125–156

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Peter D, Roghani A, Schuldiner S, Prive GG, Eisenberg D, Brecha N, Edwards RH (1992) A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter. Cell 70:539–551

    Article  PubMed  CAS  Google Scholar 

  • Lowe AW, Madeddu L, Kelly RB (1988) Endocrine secretory granules and neuronal synaptic vesicles have three integral membrane proteins in common. J Cell Biol 106:51–59

    Article  PubMed  CAS  Google Scholar 

  • Lilthi A, Di Paolo G, Cremona O, Daniell L, De Camilli P, McCormick DA (2001) Synaptojanin 1 contributes to maintaining the stability of GABAergic transmission in primary cultures of cortical neurons. J Neurosci 21:9101–9111

    Google Scholar 

  • Mackler JM, Drummond JA, Loewen CA, Robinson IM, Reist NE (2002) The C2B Ca2+-binding motif of synaptotagmin is required for synaptic transmission in vivo. Nature 418:340–344

    Article  PubMed  CAS  Google Scholar 

  • Matsushita K, Wakamori M, Rhyu IJ, Arii T, Oda S, Mori Y, Imoto K (2002) Bidirectional alterations in cerebellar synaptic transmission of tottering and rolling Ca2+ channel mutant mice. J Neurosci 22:4388–4398

    PubMed  CAS  Google Scholar 

  • Maycox PR, Hell JW, Jahn R (1990) Amino acid neurotransmission: spotlight on synaptic vesicles. Trends Neurosci 13:83–87

    Article  PubMed  CAS  Google Scholar 

  • McIntire SL, Reimer RJ, Schuske K, Edwards RH, Jorgensen EM (1997) Identification and characterization of the vesicular GABA transporter. Nature 389:870–876

    Article  PubMed  CAS  Google Scholar 

  • McMahon HT, Bolshakov VY, Janz R, Hammer RE, Siegelbaum SA, Südhof TC (1996) Synaptophysin, a major synaptic vesicle protein, is not essential for neurotransmitter release. Proc Natl Acad Sci USA 93:4760–4764

    Article  PubMed  CAS  Google Scholar 

  • Misura KM, Scheller RH, Weis WI (2000) Three-dimensional structure of the neuronal-Sec1-syntaxin 1a complex. Nature 404:355–362

    Article  PubMed  CAS  Google Scholar 

  • Mori Y, Wakamori M, Oda S, Fletcher CF, Sekiguchi N, Mori E, Copeland NG, Jenkins NA, Matsushita K, Matsuyama Z, Imoto K (2000) Reduced voltage sensitivity of activation of P/Q-type Ca2+ channels is associated with the ataxic mouse mutation rolling Nagoya (tg(rol)). J Neurosci 20:5654–5662

    PubMed  CAS  Google Scholar 

  • Murthy VN, Stevens CF (1998) Synaptic vesicles retain their identity through the endocytic cycle. Nature 392:497–501

    Article  PubMed  CAS  Google Scholar 

  • Ni B, Rosteck PR Jr, Nadi NS, Paul SM (1994) Cloning and expression of a cDNA encoding a brain-specific Na+-dependent inorganic phosphate cotransporter. Proc Natl Acad Sci USA 91:5607–5611

    Article  PubMed  CAS  Google Scholar 

  • Oheim M, Stiihmer W (2000) Tracking chromaffin granules on their way through the actin cortex. Eur Biophys J 29:67–89

    Article  PubMed  CAS  Google Scholar 

  • Ostermeier C, Brunger AT (1999) Structural basis of Rab effector specificity: crystal structure of the small G protein Rab3A complexed with the effector domain of rabphilin-3A. Cell 96:363–374

    Article  PubMed  CAS  Google Scholar 

  • Palmiter RD, Cole TB, Quaife CJ, Findley SD (1996) ZnT-3, a putative transporter of zinc into synaptic vesicles. Proc Natl Acad Sci USA 93:14934–14939

    Article  PubMed  CAS  Google Scholar 

  • Pyle JL, Kavalali ET, Piedras-Renteria ES, Tsien RW (2000) Rapid reuse of readily releasable pool vesicles at hippocampal synapses. Neuron 28:221–231

    Article  PubMed  CAS  Google Scholar 

  • Reim K, Mansour M, Varoqueaux F, McMahon HT, Südhof TC, Brose N, Rosenmund C (2001) Complexins regulate a late step in Ca2+-dependent neurotransmitter release. Cell 104:71–81

    Article  PubMed  CAS  Google Scholar 

  • Reimer RJ, Fon EA, Edwards RH (1998) Vesicular neurotransmitter transport and the presynaptic regulation of quantal size. Curr Opin Neurobiol 8:405–412

    Article  PubMed  CAS  Google Scholar 

  • Rhee JS, Betz A, Pyott S, Reim K, Varoqueaux F, Augustin I, Hesse D, Südhof TC, Takahashi M, Rosenmund C, Brose N (2002) Beta phorbol ester-and diacylglycerolinduced augmentation of transmitter release is mediated by Munc13 s and not by PKCs. Cell 108:121–133

    Article  PubMed  CAS  Google Scholar 

  • Richmond JE, Davis WS, Jorgensen EM (1999) UNC-13 is required for synaptic vesicle fusion in C. elegans. Nat Neurosci 2:959–964

    Article  PubMed  CAS  Google Scholar 

  • Richmond JE, Weimer RM, Jorgensen EM (2001) An open form of syntaxin bypasses the requirement for UNC-13 in vesicle priming. Nature 412:338–341

    Article  PubMed  CAS  Google Scholar 

  • Ringstad N, Gad H, Löw P, DiPaolo G, Brodin L, Shupliakov O, De Camilli P (1999) Endophilin/SH3P4 is required for the transition from early to late stages in clathrin-mediated synaptic vesicles endocytosis. Neuron 24:143–154

    Article  PubMed  CAS  Google Scholar 

  • Robinson IM, Ranjan R, Schwarz TL (2002) Synaptotagmins I and IV promote transmitter release independently of Ca2+ binding in the C2A domain. Nature 418:336–340

    Article  PubMed  CAS  Google Scholar 

  • Rosahl TW, Geppert M, Spillane D, Herz J, Hammer RE, Malenka RC, Südhof TC (1993) Short-term synaptic plasticity is altered in mice lacking synapsin I. Cell 75:661–670.

    Article  PubMed  CAS  Google Scholar 

  • Rosahl TW, Spillane D, Missler M, Herz J, Selig DK, Wolff JR, Hammer RE, Malenka RC, Südhof TC (1995) Essential functions of synapsins I and II in synaptic vesicle regulation. Nature 375:488–493

    Article  PubMed  CAS  Google Scholar 

  • Rosenmund C, Sigler A, Augustin I, Reim K, Brose N, Rhee JS (2002) Differential control of vesicle priming and short-term plasticity by Munc13 isoforms. Neuron 33:411–424

    Article  PubMed  CAS  Google Scholar 

  • Saegusa H, Kurihara T, Zong S, Kazuno A, Matsuda Y, Nonaka T, Han W, Toriyama H, Tanabe T (2001) Suppression of inflammatory and neuropathic pain symptoms in mice lacking the N-type Ca2+ channel. EMBO J 20:2349–2356

    Article  PubMed  CAS  Google Scholar 

  • Saegusa H, Kurihara T, Zong S, Minowa O, Kazuno A, Han W, Matsuda Y, Yamanaka H, Osanai M, Noda T, Tanabe T (2000) Altered pain responses in mice lacking alpha 1E subunit of the voltage-dependent Ca2+ channel. Proc Natl Acad Sci USA 97:6132–6137

    Article  PubMed  CAS  Google Scholar 

  • Sagne C, El Mestikawy S, Isambert MF, Hamon M, Henry JP, Giros B, Gasnier B (1997) Cloning of a functional vesicular GABA and glycine transporter by screening of genome databases. FEBS Lett 417:177–183

    Article  PubMed  CAS  Google Scholar 

  • Sakaguchi G, Manabe T, Kobayashi K, Orita S, Sasaki T, Naito A, Maeda M, Igarashi H, Katsuura G, Nishioka H, Mizoguchi A, Itohara S, Takahashi T, Takai Y (1999) Doc2alpha is an activity-dependent modulator of excitatory synaptic transmission. Eur J Neurosci 11:4262–4268

    Article  PubMed  CAS  Google Scholar 

  • Schikorski T, Stevens CF (2001) Morphological correlates of functionally defined synaptic vesicle populations. Nat Neurosci 4:391–395

    Article  PubMed  CAS  Google Scholar 

  • Schlüter OM, Schnell E, Verhage M, Tzonopoulos T, Nicoll RA, Janz R, Malenka RC, Geppert M, Südhof TC (1999) Rabphilin knockout mice reveal that rabphilin is not required for rab3 function in regulating neurotransmitter release. J Neurosci 19:5834–5846

    PubMed  Google Scholar 

  • Schmid SL (1997) Clathrin-coated vesicle formation and protein sorting: an integrated process. Annu Rev Biochem 66:511–548

    Article  PubMed  CAS  Google Scholar 

  • Schmid SL, McNiven MA, De Camilli P (1998) Dynamin and its partners: a progress report. Curr Opin Cell Biol 10:504–512

    Article  PubMed  CAS  Google Scholar 

  • Schmidt A, Wolde M, Thiele C, Fest W, Kratzin H, Podtelejnikov AV, Witke W, Huttner WB, Söling HD (1999) Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid. Nature 401:133–141

    Article  PubMed  CAS  Google Scholar 

  • Schneggenburger R, Neher E (2000) Intracellular calcium dependence of transmitter release rates at a fast central synapse. Nature 406:889–893

    Article  PubMed  CAS  Google Scholar 

  • Schoch S, Castillo PE, Jo T, Mukherjee K, Geppert M, Wang Y, Schmitz F, Malenka RC, Südhof TC (2002) RIM1alpha forms a protein scaffold for regulating neurotransmit-ter release at the active zone. Nature 415:321–326

    Article  PubMed  CAS  Google Scholar 

  • Schoch S, Deak F, Konigstorfer A, Mozhayeva M, Sara Y, Südhof TC, Kavalali ET (2001) SNARE function analyzed in synaptobrevin/VAMP knockout mice. Science 294:1117–1122

    Article  PubMed  CAS  Google Scholar 

  • Silva AJ, Rosahl TW, Chapman PF, Marowitz Z, Friedman E, Frankland PW, Cestari V, Cioffi D, Südhof TC, Bourtchuladze R (1996) Impaired learning in mice with abnormal short-lived plasticity. Curr Biol 6:1509–1518

    Article  PubMed  CAS  Google Scholar 

  • Sorensen JB, Matti U, Wei SH, Nehring RB, Voets T, Ashery U, Binz T, Neher E, Rettig J (2002) The SNARE protein SNAP-25 is linked to fast calcium triggering of exocytosis. Proc Natl Acad Sci USA 99:1627–1632

    Article  PubMed  CAS  Google Scholar 

  • Spiwoks-Becker I, Vollrath L, Seeliger MW, Jaissle G, Eshkind LG, Leube RE (2001) Synaptic vesicle alterations in rod photoreceptors of synaptophysin-deficient mice. Neuroscience 107:127–142

    Article  PubMed  CAS  Google Scholar 

  • Stevens CF, Williams JH (2000) “Kiss and run” exocytosis at hippocampal synapses. Proc Natl Acad Sci USA 97:12828–12832

    Article  PubMed  CAS  Google Scholar 

  • Stevens TH, Forgac M (1997) Structure, function and regulation of the vacuolar (H+)-AT-Pase. Annu Rev Cell Dev Biol 13:779–808

    Article  PubMed  CAS  Google Scholar 

  • Steyer JA, Almers W (1999) Tracking single secretory granules in live chromaffin cells by evanescent-field fluorescence microscopy. Biophys J 76:2262–2271

    Article  PubMed  CAS  Google Scholar 

  • Stobrawa SM, Breiderhoff T, Takamori S, Engel D, Schweizer M, Zdebik AA, Bosl MR, Ruether K, Jahn H, Draguhn A, Jahn R, Jentsch TJ (2001) Disruption of ClC-3, a chloride channel expressed on synaptic vesicles, leads to a loss of the hippocampus. Neuron 29:185–196

    Article  PubMed  CAS  Google Scholar 

  • Südhof TC (2000) The synaptic vesicle cycle revisited. Neuron 28:317–320

    Article  PubMed  Google Scholar 

  • Südhof TC (2002) Synaptotagmins: why so many? J Biol Chem 277:7629–7632

    Article  PubMed  CAS  Google Scholar 

  • Südhof TC, De Camilli P, Niemann H, Jahn R (1993) Membrane fusion machinery: insights from synaptic proteins. Cell 75:1–4

    PubMed  Google Scholar 

  • Sutton RB, Fasshauer D, Jahn R, Brunger AT (1998) Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution. Nature 395:347–353

    Article  PubMed  CAS  Google Scholar 

  • Takahashi N, Miner LL, Sora I, Ujike H, Revay RS, Kostic V, Jackson-Lewis V, Przedborski S, Uhl GR (1997) VMAT2 knockout mice: heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity. Proc Natl Acad Sci USA 94:9938–9943

    Article  PubMed  CAS  Google Scholar 

  • Takahashi S, Ujihara H, Huang GZ, Yagyu KI, Sanbo M, Kaba H, Yagi T (1999) Reduced hippocampal LTP in mice lacking a presynaptic protein: complexin II. Eur J Neurosci 11:2359–2366

    Article  PubMed  CAS  Google Scholar 

  • Takamori S, Rhee JS, Rosenmund C, Jahn R (2001) Identification of differentiation-associated brain-specific phosphate transporter as a second vesicular glutamate transporter (VGLUT2). J Neurosci 21:RC182

    PubMed  CAS  Google Scholar 

  • Takei K, Slepnev VI, Haucke V, De Camilli P (1999) Functional partnership between amphiphysin and dynamin in clathrin-mediated endocytosis. Nat Cell Biol 1:33–39

    Article  PubMed  CAS  Google Scholar 

  • Tanaka M, Miyoshi J, Ishizaki H, Togawa A, Ohnishi K, Endo K, Matsubara K, Mizoguchi A, Nagano T, Sato M, Sasaki T, Takai (2001) Role of Rab3 GDP/GTP exchange protein in synaptic vesicle trafficking at the mouse neuromuscular junction. Mol Biol Cell 12:1421–1430

    PubMed  CAS  Google Scholar 

  • Tarsa L, Goda Y (2002) Synaptophysin regulates activity-dependent synapse formation in cultured hippocampal neurons. Proc Natl Acad Sci 99:1012–1016

    Article  PubMed  CAS  Google Scholar 

  • Terada S, Tsujimoto T, Takei Y, Takahashi T, Hirokawa N (1999) Impairment of inhibitory synaptic transmission in mice lacking synapsin I. J Cell Biol 145:1039–1048

    Article  PubMed  CAS  Google Scholar 

  • Tobaben S, Südhof TC, Stahl B (2002) Genetic analysis of alpha-latrotoxin receptors reveals functional interdependence of CIRL/latrophilin 1 and neurexin 1 alpha. J Biol Chem 277:6359–6365.

    Article  PubMed  CAS  Google Scholar 

  • Tobaben S, Thakur P, Fernandez-Chacon R, Südhof TC, Rettig J, Stahl B (2001) A trimeric protein complex functions as a synaptic chaperone machine. Neuron 31:987–999

    Article  PubMed  CAS  Google Scholar 

  • Travis ER, Wang YM, Michael DJ, Caron MG, Wightman RM (2000) Differential quantal release of histamine and 5-hydroxytryptamine from mast cells of vesicular monoamine transporter 2 knockout mice. Proc Natl Acad Sci USA 97:162–167

    Article  PubMed  CAS  Google Scholar 

  • Uhl GR, Li S, Takahashi N, Itokawa K, Lin Z, Hazama M, Sora I (2000) The VMAT2 gene in mice and humans: amphetamine responses, locomotion, cardiac arrhythmias, aging, and vulnerability to dopaminergic toxins. FASEB J 14:2459–2465

    Article  PubMed  CAS  Google Scholar 

  • Ungewickell E (1999) Wrapping the package. Proc Natl Acad Sci USA 96:8809–8810

    Article  PubMed  CAS  Google Scholar 

  • Varoqueaux F, Sigler A, Rhee JS, Brose N, Enk C, Reim K, Rosenmund C (2002) Total arrest f spontaneous and evoked synaptic transmission but normal synaptogenesis in the absence of Munc13-mediated vesicle priming. Proc Natl Acad Sci USA 99:9037–9042

    Article  PubMed  CAS  Google Scholar 

  • Verhage M, Maia AS, Plomp JJ, Brussaard AB, Heeroma JH, Vermeer H, Toonen RF, Hammer RE, van den Berg TK, Missler M, Geuze HJ, Südhof TC (2000) Synaptic assembly of the brain in the absence of neurotransmitter secretion. Science 287:864–869

    Article  PubMed  CAS  Google Scholar 

  • Voets T, Toonen RF, Brian EC, de Wit H, Moser T, Rettig J, Südhof TC, Neher E, Verhage M (2001) Munc18-1 promotes large dense-core vesicle docking. Neuron 31:581–591

    Article  PubMed  CAS  Google Scholar 

  • Wang YM, Gainetdinov RR, Fumagalli F, Xu F, Jones SR, Bock CB, Miller GW, Wightman RM, Caron MG (1997) Knockout of the vesicular monoamine transporter 2 gene results in neonatal death and supersensitivity to cocaine and amphetamine. Neuron 19:1285–1296

    Article  PubMed  CAS  Google Scholar 

  • Washbourne P, Thompson PM, Carta M, Costa ET, Mathews JR, Lopez-Bendito G, Molnar Z, Becher MW, Valenzuela CF, Partridge LD, Wilson MC (2002) Genetic ablation of the t-SNARE SNAP-25 distinguishes mechanisms of neuroexocytosis. Nat Neurosci 5:19–26

    PubMed  CAS  Google Scholar 

  • Weber T, Zemelman BV, McNew JA, Westermann B, Gmachl M, Parlati F, Sollner TH, Rothman JE (1998) SNAREpins: minimal machinery for membrane fusion. Cell 92:759–772

    Article  PubMed  CAS  Google Scholar 

  • Xu T, Bajjalieh SM (2001) SV2 modulates the size of the readily releasable pool of secretory vesicles. Nat Cell Biol 3:691–698

    Article  PubMed  CAS  Google Scholar 

  • Zwingman TA, Neumann PE, Noebels JL, Herrup K (2001) Rocker is a new variant of the voltage-dependent calcium channel gene Cacna1a. J Neurosci 21:1169–1178

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Abteilung Molekulare Neurobiologie, Max-Planck-Institut für Experimentelle Medizin, Herrmann-Rein-Straße 3, 37075, Göttingen, Germany

    N. Brose

  2. Physiologisches Institut, Universität des Saarlandes, Gebäude 59, 66424, Homburg, Germany

    J. Rettig

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  1. N. Brose
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Correspondence to N. Brose .

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  1. Pharmakologisches Institut, Universität Heidelberg, Im Neuenheimer Feld 366, 69120, Heidelberg, Germany

    Stefan Offermanns

  2. Institut für Pharmakologie und Toxikologie der Universität, Versbacher Straße 9, 97078, Germany

    Lutz Hein

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Brose, N., Rettig, J. (2004). Transgenic Mouse Models in the Analysis of Neurotransmitter Release Mechanisms. In: Offermanns, S., Hein, L. (eds) Transgenic Models in Pharmacology. Handbook of Experimental Pharmacology, vol 159. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18934-0_8

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  • DOI: https://doi.org/10.1007/978-3-642-18934-0_8

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