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INIZIO_TESTO_DA_INDICIZZARE

Fund for investing in fundamental research

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Research Units
  • Universita' degli Studi di GENOVA
    Dip. MEDICINA SPERIMENTALE , GENOVA (GE)
  • Libera Universita' "Vita Salute S.Raffaele" MILANO
    Dip. NEUROSCIENZE , MILANO (MI)
  • Universita' degli Studi di GENOVA
    Dip. MEDICINA SPERIMENTALE , GENOVA (GE)
  • Universita' degli Studi di GENOVA
    Dip. MEDICINA SPERIMENTALE , GENOVA (GE)
  • Universita' degli Studi di TORINO
    Dip. NEUROSCIENZE , TORINO (TO)
  • Universit¿ degli Studi di GENOVA
    ONCOLOGIA, BIOLOGIA E GENETICA , GENOVA (GE)
  • Consiglio nazionale delle ricerche (CNR)
    Istituto di Cibernetica e Biofisica , GENOVA (GE)
Similar FIRB:
Scientific and education field classification
International Patent Classification
  • CHEMISTRY; METALLURGY
    • BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
      • MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF (biocides, pest repellants or attractants, or plant growth regulators, containing micro-organisms, viruses, microbial fungi, enzymes, fermentates or substances produced by or extracted from micro-organisms or animal material A01N63/00; food compositions A21, A23; medicinal preparations A61K; chemical aspects of, or use of materials for, bandages, dressings, absorbent pads or surgical articles A61L; fertilisers C05); PROPAGATING, PRESERVING OR MAINTAINING MICRO-ORGANISMS (preservation of living parts of humans or animals A01N1/02); MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (micro-biological testing media C12Q)
Geographical classification
Bibliografia
1. Ancolio K., Dumanchin C., Barelli H., Warter J.M., Brice A., Campion D., Frebourg T., Checler F. (1999) Proc. Natl. Acad. Sci. USA 96, 4119-4124
2. Araque A., Carmignoto G., Haydon P.G. (2001) Annu. Rev. Physiol. 63, 795-813
3. Benfenati F., Valtorta F., Chieregatti E., Greengard P. (1992) Neuron 8, 377-386
4. Benfenati F., Valtorta F., Rossi M.C., Onofri F., Sihra T.S., Greengard P. (1993) J. Cell Biol. 123, 1845-1855
5. Berg E.A., Johnson R.J., Leeman S.E., Boyd N., Kimerer L., Fine R.E. (2000) J. Neurosci. Res. 62, 830-839
6. Berger-Sweeney J., McPhie D.L., Arters J.A., Greenan J., Oster-Granite M.L., Neve R.L. (1999) Mol. Brain Res. 66, 150-162
7. Bonanno G. and Raiteri M. (1994) Prog. Neurobiol. 44, 451-462
8. Bravin M., Morando L., Vercelli A., Rossi F., Strata P. (1999) Proc. Natl. Acad. Sci. USA 96, 1704-1709
9. Brodin L., Löw P., Gad H., Gustafsson J., Pieribone V.A., Shupliakov O. (1997) Eur. J. Neurosci. 9, 2503-2511
10. Busetto G., Buffelli M., Toganna E., Bellico F., Cangiano A. (2000) J. Neurosci. 20, 685-695
11. Ceccaldi P.E., Grohovaz F., Benfenati F., Chieregatti E., Greengard P., Valtorta F. (1995) J. Cell Biol. 128, 905-912
12. Cheetam J.J., Hilfiker S., Benfenati F., Weber T., Greengard P., Czernik A.J. (2001) Biochem. J. 354, 57-66
13. Cheramy A., Godeheu G., L'Hirondel M., Glowinski J. (1996) J. Pharmacol. Exp. Ther. 276, 616-625
14. Cupers P., Bentahir M., Craessaerts K., Orlans I., Vanderstichele H., Saftig P., De Strooper B., Annaert W. (2001) J. Cell Biol. 154, 731-740
15. Ensoli B., Buonaguro L., Barillari G., Fiorelli V., Gendelman R., Morgan R.A. (1993) J. Virol. 67, 277-287
16. Facchiano F., Benfenati F., Valtorta F., Luini A. (1993) J. Biol Chem. 268, 4588-4591
17. Franke H., Krugel U., Illes P. (1999) Glia 28, 190-200
18. Gavazzo P., Gazzoli A., Mazzolini M., Marchetti C. (2001) Neuroreport 12, 3121-3125
19. Greengard P., Valtorta F., Czernik A.J., Benfenati F. (1993) Science 259, 780-785
20. Guilarte T.R. (1997) Neurotoxicology 18, 665-672
21. Haass C. and De Strooper B. (1999) Science 286 (5441) 916-919
22. Hansel C. and Linden D. J. (2000) Neuron 26, 473-482
23. Haughey N.J., Nath A., Mattson M.P., Slevin J.T., Geiger J.D. (2001) J. Neurochem. 78, 457-467
24. Hilfiker S., Schweizer F.E., Kao H.-T., Czernik A.J., Greengard P., Augustine G.J. (1998) Nature Neurosci. 1, 29-35
25. Hori O., Brett J. et al. (1995) J. Biol. Chem. 270, 25752-25761
26. Hosaka M. and Südhof T.C. (1998) J. Biol. Chem. 273, 1425-1429
27. Li L., Chin L.-S., Shupliakov O., Brodin L., Sihra T.S., Hvalby Ø., Jensen V., Zheng D., McNamara J.O., Greengard P., Andersen P. (1995) Proc. Natl. Acad. Sci. USA 92, 9235-9239
28. Low C.M., Zheng F., Lyuboslavsky P., Traynelis S.F. (2000) Proc. Natl. Acad. Sci. USA 97, 11062-11067
29. MacManus A., Ramsden M., Murray M., Henderson Z., Pearson H.A., Campbell V.A. (2000) J. Biol. Chem. 275, 4713-4718
30. Mariani J. and Changeux J.-P. (1981) J. Neurosci. 1, 696-702
31. Merenmies J., Pihlaskari R., Laitinen J., Wartiovaara J., Rauvala H. (1991) J. Biol Chem. 266, 16722-16729
32. Morando L., Cesa R., Rasetti R., Harvey R., Strata P. (2001) Proc. Natl. Acad. Sci. USA 98, 9954-9959
33. Neary J.T., Rathbone M.P., Cattabeni F., Abbracchio M.P., Burbstock G. (1996) Trends Neurosci. 19, 13-18
34. Norenberg M.D. (1994) J. Neuropathol. Exp. Neurol. 53, 213-220
35. Okamoto M., Nakajima Y., Matsuyama T., Sugita M. (2001) Neuroscience 104, 653-665
36. Oster-Granite M.L., McPhie D.L., Greenan J., Neve R.L. (1996) J. Neurosci. 16, 6732-6741
37. Passalacqua M., Patrone M., Picotti G.B., Del Rio M., Sparatore B., Melloni E., Pontremoli S. (1998) 82, 1021-1028
38. Pieribone V.A., Shupliakov O., Brodin L., Hilfiker-Rothenfluh S., Czernik A.J., Greengard P. (1995) Nature 375, 493-497
39. Pittaluga A., Bonfanti A., Raiteri M. (1997) Naunyn-Schmiedeb. Arch. Pharmacol. 356, 29-38
40. Pittaluga A.,Feligioni M., Ghersi C., Gemignani A., Raiteri M. (2001) Neuropharmacology 41, 301-310
41. Raiteri L and Raiteri M. (2000) Neurochem. Res. 25, 1265-1274
42. Raiteri L., Raiteri M., Bonanno G. (2001) J. Neurochem. 76, 1823-1832
43. Raiteri M. (2001) J. Neurochem. 78, 673-675
44. Raiteri M., Angelini F., Levi G. (1974) Eur. J. Pharmacol. 25, 411-414
45. Raiteri M., Garrone B., Pittaluga A. (1992) J. Pharmacol. Exp. Ther 260, 238-242
46. Rosahl T.W., Spillane D., Missler M., Herz J., Selig D.K., Wolff J.R., Hammer R.E., Malenka R.C., Südhof T.C. (1995) Nature 375, 488-493
47. Rossi F. and Strata P. (1995) Prog. Neurobiol. 47, 341-369
48. Russo C., Saido T.C., DeBusk L.M., Tabatono M. Gambetti P., Teller J.K. (1997) FEBS Letters 409, 411-416
49. Russo C., Schettini G., Saido T.C., Hulette C., Lippall C., Lannfelt L., Ghetti B., Gambetti P., Tabaton M., Teller J.K. (2000) Nature 405 (6786) 531-532
50. Russo C., Salis S., Dolcini V., Venezia V., Song X.H., Teller J.K., Schettini G. (2001) Neurobiol. Disease 8, 173-180
51. Sacchetti B., Lorenzini C.A., Baldi E., Tassoni G., Bucherelli C. (1999) J. Neurosci. 19, 9570-9578
52. Saido T.C., Iwatsubo T., Mann D.M., Shimada H., Ihara Y., Kawashima S. (1995) Neuron 14, 457-466
53. Selkoe D. J. (2001) Physiol. Rev. 81, 741-766
54. Shupliakov O., Low P., Grabs D., Gad H., Chen H., David C., Takei K., De Camilli P., Brodin L. (1997) Science 276 (5310) 259-163
55. Sivadon P., Bauer F., Aigle M., Crouzet M. (1995) Mol. Gen. Genet 246, 485-495
56. Slepnev V.I., Ochoa G.C., Butler M.H., De Camilli P. (2000) J. Biol. Chem. 275, 17583-17589
57. Sparatore B., Patrone M., Passalacqua M., Pedrazzi M., Gaggero D., Pontremoli S., Melloni E. (2001) Biochem. J. 357, 569-574
58. Starke K., GöthertM., Kilbinger H. (1989) Physiol. Rev. 69, 864-989
59. Stobrawa S.M., Breiderhoff T. et al. (2001) Neuron 29, 185-196
60. Taguchi A., Blood D.C. et al. (2000) Nature 405, 354-360
61. Takei K., Slepnev V.I., Haucke V., De Camilli P. (1999) Nat. Cell Biol. 1, 33-39
62. Valtorta F., Iezzi N., Benfenati F., Lu B., Poo M-m, Greengard P. (1995) Eur. J. Neurosci. 7, 261-270
63. Vassar R., Bennett B.D. et al. (1999) Science 286 (5440) 735-741
64. Vizi E.S. and Kiss J.P. (1998) Hippocampus 8, 566-607
65. Wang H.C., Bloom O. et al. (1999) 285, 248-251
66. Wigge P., Vallis Y., McMahon H.T. (1997) Curr. Biol. 7, 554-560
67. Wigge P. and McMahon H.T. (1998) Trends Neurosci. 21, 339-344
68. Zambrano N., Buxbaum J.D., et al. (1997) J. Biol. Chem. 272, 6399-6405
69. Zambrano N., Bruni P., Minopoli G., Mosca R., Molino D., Russo C., Schettini G., Sudol M., Russo T. (2000) J. Biol. Chem. 276, 19787-19792
Keywords
Synaptic proteins; Protein-ptrotein interaction; Neurotransmitter release; Synaptic plasticity; Glia-neuron communication; Neurodegeneration

Functional interactions among synaptic proteins: physiopathology and potential therapeutic indications.

Università degli Studi di Genova
Abstract
Information transfer in the nervous system is emerging as an extreme complex process. An increasing number of actors, especially proteins, seem to play a role through interactions that are still poorly understood. Similarly, the search of novel therapeutic tools and strategies for neuropsychiatric disorders still awaits the identification and characterization of new molecular targets at the synaptic level. Clearly, if synaptic proteins (receptors, transporters, transducing systems, ion channels, etc.) work as multimers rather than as individual molecules, novel therapeutic targets may originate from the detailed knowledge of the interactions in which these proteins are engaged. Thus, our future aim will be the development of drugs not exclusively directed against a single protein, but that are able to correct the faulty functions of interacting protein complexes. To reach this goal, our knowledge of the functional proteomics of the synapse needs to be enriched under both physiological and pathological aspects. The project has four specific aims:
AIM 1. To characterize of the protein-protein interactions involved in synaptic vesicle trafficking and exocytosis under physiological conditions and in genetic models of deficits of synaptic transmission. These studies identify and characterize the regulation of the expression of genes coding for the proteins of interest, their mechanisms of targeting to the synapse, the stepwise assembly of synapses and their functional>>>

Principal Investigator
MAURIZIO RAITERI, Universita' degli Studi di GENOVA
Research Goal
AIM 1. CHARACTERIZATION OF THE PROTEIN-PROTEIN INTERACTIONS INVOLVED IN SYNAPTIC VESICLE TRAFFICKING AND EXOCYTOSIS UNDER PHYSIOLOGICAL CONDITIONS AND IN GENETIC MODELS OF DEFICITS OF SYNAPTIC TRANSMISSION
1.1 To study synaptic vesicles biogenesis in immature neurons by analyzing the proteins involved in synaptic exo-endocytosis. Specific points include: the developmental regulation of expression of genes coding for the proteins of interest, their mechanisms of targeting to the synapse, the stepwise assembly of synapses and the properties.
1.2 To characterize knock-out mice for amphiphysin 1, the best characterized accessory factor of clathrin-dependent recycling at the synapse. Amphiphysin function in synaptic vesicle recycling is supported by several evidences, including dominant negative interference studies. Furthermore, yeast genetics implicate amphiphysin also in actin cytoskeleton dynamics. Specific aims are (i) to identify the specific step(s) at which amphiphysin 1 is implicated in synaptic vesicle recycling and (ii) to explore actin function in endocytosis.
1.3 To identify the interactions mediated by the highly conserved domains A, C and E of the synapsins. Short peptide sequences from within each of the highly conserved domains of synapsins have been shown to regulate neurotransmitter release. We hypothesize that the activity of each peptide is mediated through interactions with novel synapsin binding partners. Novel binding partners for>>>

Timescale
36 months