Skip to main content
SpringerLink
Log in

The role of synapsins in neuronal development

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

The synapsins, the first identified synaptic vesicle-specific proteins, are phosphorylated on multiple sites by a number of protein kinases and are involved in neurite outgrowth and synapse formation as well as in synaptic transmission. In mammals, the synapsin family consists of at least 10 isoforms encoded by 3 distinct genes and composed by a mosaic of conserved and variable domains. The synapsins are highly conserved evolutionarily, and orthologues have been found in invertebrates and lower vertebrates. Within nerve terminals, synapsins are implicated in multiple interactions with presynaptic proteins and the actin cytoskeleton. Via these interactions, synapsins control several mechanisms important for neuronal homeostasis. In this review, we describe the main functional features of the synapsins, in relation to the complex role played by these phosphoproteins in neuronal development.

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

Access this article

Log in via an institution

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
Fig. 6

Similar content being viewed by others

References

  1. De Camilli P, Benfenati F, Valtorta F, Greengard P (1990) The synapsins. Annu Rev Cell Biol 6:433–460

    Article  PubMed  Google Scholar 

  2. Greengard P, Valtorta F, Czernik AJ, Benfenati F (1993) Synaptic vesicle phosphoproteins and regulation of synaptic function. Science 259:780–785

    Article  PubMed  CAS  Google Scholar 

  3. Fdez E, Hilfiker S (2006) Vesicle pools and synapsins: new insights into old enigmas. Brain Cell Biol 35:107–115

    Article  PubMed  Google Scholar 

  4. De Camilli P, Cameron R, Greengard P (1983) Synapsin I (protein I), a nerve terminal-specific phosphoprotein. I. Its general distribution in synapses of the central and peripheral nervous system demonstrated by immunofluorescence in frozen and plastic sections. J Cell Biol 96:1337–1354

    Article  PubMed  Google Scholar 

  5. De Camilli P, Harris SM Jr, Huttner WB, Greengard P (1983) Synapsin I (protein I), a nerve terminal-specific phosphoprotein. II. Its specific association with synaptic vesicles demonstrated by immunocytochemistry in agarose-embedded synaptosomes. J Cell Biol 96:1355–1373

    Article  PubMed  Google Scholar 

  6. 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

    Article  PubMed  CAS  Google Scholar 

  7. Benfenati F, Bahler M, Jahn R, Greengard P (1989) Interactions of synapsin I with small synaptic vesicles: distinct sites in synapsin I bind to vesicle phospholipids and vesicle proteins. J Cell Biol 108:1863–1872

    Article  PubMed  CAS  Google Scholar 

  8. Benfenati F, Valtorta F, Rubenstein JL, Gorelick FS, Greengard P, Czernik AJ (1992) Synaptic vesicle-associated Ca2+/calmodulin-dependent protein kinase II is a binding protein for synapsin I. Nature 359:417–420

    Article  PubMed  CAS  Google Scholar 

  9. Ferreira A, Kao HT, Feng J, Rapoport M, Greengard P (2000) Synapsin III: developmental expression, subcellular localization, and role in axon formation. J Neurosci 20:3736–3744

    PubMed  CAS  Google Scholar 

  10. Kao HT, Li P, Chao HM, Janoschka S, Pham K, Feng J, McEwen BS, Greengard P, Pieribone VA, Porton B (2008) Early involvement of synapsin III in neural progenitor cell development in the adult hippocampus. J Comp Neurol 507:1860–1870

    Article  PubMed  CAS  Google Scholar 

  11. Bahler M, Greengard P (1987) Synapsin I bundles F-actin in a phosphorylation-dependent manner. Nature 326:704–707

    Article  PubMed  CAS  Google Scholar 

  12. Benfenati F, Valtorta F, Chieregatti E, Greengard P (1992) Interaction of free and synaptic vesicle-bound synapsin I with F-actin. Neuron 8:377–386

    Article  PubMed  CAS  Google Scholar 

  13. Valtorta F, Greengard P, Fesce R, Chieregatti E, Benfenati F (1992) Effects of the neuronal phosphoprotein synapsin I on actin polymerization. I. Evidence for a phosphorylation-dependent nucleating effect. J Biol Chem 267:11281–11288

    PubMed  CAS  Google Scholar 

  14. Baldelli P, Fassio A, Valtorta F, Benfenati F (2007) Lack of synapsin I reduces the readily releasable pool of synaptic vesicles at central inhibitory synapses. J Neurosci 27:13520–13531

    Article  PubMed  CAS  Google Scholar 

  15. Valtorta F, Benfenati F, Greengard P (1992) Structure and function of the synapsins. J Biol Chem 267:7195–7198

    PubMed  CAS  Google Scholar 

  16. Ceccaldi PE, Grohovaz F, Benfenati F, Chieregatti E, Greengard P, Valtorta F (1995) Dephosphorylated synapsin I anchors synaptic vesicles to actin cytoskeleton: an analysis by videomicroscopy. J Cell Biol 128:905–912

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  18. 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 

  19. Gitler D, Takagishi Y, Feng J, Ren Y, Rodriguiz RM, Wetsel WC, Greengard P, Augustine GJ (2004) Different presynaptic roles of synapsins at excitatory and inhibitory synapses. J Neurosci 24:11368–11380

    Article  PubMed  CAS  Google Scholar 

  20. Siksou L, Rostaing P, Lechaire JP, Boudier T, Ohtsuka T, Fejtova A, Kao HT, Greengard P, Gundelfinger ED, Triller A, Marty S (2007) Three-dimensional architecture of presynaptic terminal cytomatrix. J Neurosci 27:6868–6877

    Article  PubMed  CAS  Google Scholar 

  21. Hilfiker S, Schweizer FE, Kao HT, Czernik AJ, Greengard P, Augustine GJ (1998) Two sites of action for synapsin domain E in regulating neurotransmitter release. Nat Neurosci 1:29–35

    Article  PubMed  CAS  Google Scholar 

  22. Hilfiker S, Benfenati F, Doussau F, Nairn AC, Czernik AJ, Augustine GJ, Greengard P (2005) Structural domains involved in the regulation of transmitter release by synapsins. J Neurosci 25:2658–2669

    Article  PubMed  CAS  Google Scholar 

  23. Fassio A, Merlo D, Mapelli J, Menegon A, Corradi A, Mete M, Zappettini S, Bonanno G, Valtorta F, D’Angelo E, Benfenati F (2006) The synapsin domain E accelerates the exo-endocytotic cycle of synaptic vesicles in cerebellar Purkinje cells. J Cell Sci 119:4257–4268

    Article  PubMed  CAS  Google Scholar 

  24. Chiappalone M, Casagrande S, Tedesco M, Valtorta F, Baldelli P, Martinoia S, Benfenati F (2009) Opposite changes in glutamatergic and GABAergic transmission underlie the diffuse hyperexcitability of synapsin I-deficient cortical networks. Cereb Cortex 19:1422–1439

    Article  PubMed  Google Scholar 

  25. Kao HT, Porton B, Hilfiker S, Stefani G, Pieribone VA, DeSalle R, Greengard P (1999) Molecular evolution of the synapsin gene family. J Exp Zool 285:360–377

    Article  PubMed  CAS  Google Scholar 

  26. Esser L, Wang CR, Hosaka M, Smagula CS, Sudhof TC, Deisenhofer J (1998) Synapsin I is structurally similar to ATP-utilizing enzymes. EMBO J 17:977–984

    Article  PubMed  CAS  Google Scholar 

  27. Hosaka M, Sudhof TC (1998) Synapsins I and II are ATP-binding proteins with differential Ca2+ regulation. J Biol Chem 273:1425–1429

    Article  PubMed  CAS  Google Scholar 

  28. Hosaka M, Sudhof TC (1999) Homo- and heterodimerization of synapsins. J Biol Chem 274:16747–16753

    Article  PubMed  CAS  Google Scholar 

  29. Onofri F, Messa M, Matafora V, Bonanno G, Corradi A, Bachi A, Valtorta F, Benfenati F (2007) Synapsin phosphorylation by SRC tyrosine kinase enhances SRC activity in synaptic vesicles. J Biol Chem 282:15754–15767

    Article  PubMed  CAS  Google Scholar 

  30. Pieribone VA, Shupliakov O, Brodin L, Hilfiker-Rothenfluh S, Czernik AJ, Greengard P (1995) Distinct pools of synaptic vesicles in neurotransmitter release. Nature 375:493–497

    Article  PubMed  CAS  Google Scholar 

  31. Gitler D, Xu Y, Kao HT, Lin D, Lim S, Feng J, Greengard P, Augustine GJ (2004) Molecular determinants of synapsin targeting to presynaptic terminals. J Neurosci 24:3711–3720

    Article  PubMed  CAS  Google Scholar 

  32. Monaldi I, Vassalli M, Bachi A, Millo E, Valtorta F, Raiteri R, Benfenati F, Fassio A (2009) The highly conserved synapsin domain E mediates synapsin dimerization and phospholipid vesicle clustering. Biochem J (in press)

  33. Johnson EM, Ueda T, Maeno H, Greengard P (1972) Adenosine 3′, 5-monophosphate-dependent phosphorylation of a specific protein in synaptic membrane fractions from rat cerebrum. J Biol Chem 247:5650–5652

    PubMed  CAS  Google Scholar 

  34. Huttner WB, Greengard P (1979) Multiple phosphorylation sites in protein I and their differential regulation by cyclic AMP and calcium. Proc Natl Acad Sci USA 76:5402–5406

    Article  PubMed  CAS  Google Scholar 

  35. Czernik AJ, Pang DT, Greengard P (1987) Amino acid sequences surrounding the cAMP-dependent and calcium/calmodulin-dependent phosphorylation sites in rat and bovine synapsin I. Proc Natl Acad Sci USA 84:7518–7522

    Article  PubMed  CAS  Google Scholar 

  36. Jovanovic JN, Benfenati F, Siow YL, Sihra TS, Sanghera JS, Pelech SL, Greengard P, Czernik AJ (1996) Neurotrophins stimulate phosphorylation of synapsin I by MAP kinase and regulate synapsin I-actin interactions. Proc Natl Acad Sci USA 93:3679–3683

    Article  PubMed  CAS  Google Scholar 

  37. Matsubara M, Kusubata M, Ishiguro K, Uchida T, Titani K, Taniguchi H (1996) Site-specific phosphorylation of synapsin I by mitogen-activated protein kinase and Cdk5 and its effects on physiological functions. J Biol Chem 271:21108–21113

    Article  PubMed  CAS  Google Scholar 

  38. Jovanovic JN, Sihra TS, Nairn AC, Hemmings HC Jr, Greengard P, Czernik AJ (2001) Opposing changes in phosphorylation of specific sites in synapsin I during Ca2+-dependent glutamate release in isolated nerve terminals. J Neurosci 21:7944–7953

    PubMed  CAS  Google Scholar 

  39. Benfenati F, Neyroz P, Bahler M, Masotti L, Greengard P (1990) Time-resolved fluorescence study of the neuron-specific phosphoprotein synapsin I. Evidence for phosphorylation-dependent conformational changes. J Biol Chem 265:12584–12595

    PubMed  CAS  Google Scholar 

  40. Hosaka M, Hammer RE, Sudhof TC (1999) A phospho-switch controls the dynamic association of synapsins with synaptic vesicles. Neuron 24:377–387

    Article  PubMed  CAS  Google Scholar 

  41. Schiebler W, Jahn R, Doucet JP, Rothlein J, Greengard P (1986) Characterization of synapsin I binding to small synaptic vesicles. J Biol Chem 261:8383–8390

    PubMed  CAS  Google Scholar 

  42. Torri Tarelli F, Bossi M, Fesce R, Greengard P, Valtorta F (1992) Synapsin I partially dissociates from synaptic vesicles during exocytosis induced by electrical stimulation. Neuron 9:1143–1153

    Article  PubMed  CAS  Google Scholar 

  43. Sihra TS, Wang JK, Gorelick FS, Greengard P (1989) Translocation of synapsin I in response to depolarization of isolated nerve terminals. Proc Natl Acad Sci USA 86:8108–8112

    Article  PubMed  CAS  Google Scholar 

  44. Llinas R, McGuinness TL, Leonard CS, Sugimori M, Greengard P (1985) Intraterminal injection of synapsin I or calcium/calmodulin-dependent protein kinase II alters neurotransmitter release at the squid giant synapse. Proc Natl Acad Sci USA 82:3035–3039

    Article  PubMed  CAS  Google Scholar 

  45. Llinas R, Gruner JA, Sugimori M, McGuinness TL, Greengard P (1991) Regulation by synapsin I and Ca(2+)-calmodulin-dependent protein kinase II of the transmitter release in squid giant synapse. J Physiol 436:257–282

    PubMed  CAS  Google Scholar 

  46. Hackett JT, Cochran SL, Greenfield LJ Jr, Brosius DC, Ueda T (1990) Synapsin I injected presynaptically into goldfish mauthner axons reduces quantal synaptic transmission. J Neurophysiol 63:701–706

    PubMed  CAS  Google Scholar 

  47. Nichols RA, Sihra TS, Czernik AJ, Nairn AC, Greengard P (1990) Calcium/calmodulin-dependent protein kinase II increases glutamate and noradrenaline release from synaptosomes. Nature 343:647–651

    Article  PubMed  CAS  Google Scholar 

  48. Nichols RA, Chilcote TJ, Czernik AJ, Greengard P (1992) Synapsin I regulates glutamate release from rat brain synaptosomes. J Neurochem 58:783–785

    Article  PubMed  CAS  Google Scholar 

  49. Torri-Tarelli F, Villa A, Valtorta F, De Camilli P, Greengard P, Ceccarelli B (1990) Redistribution of synaptophysin and synapsin I during alpha-latrotoxin-induced release of neurotransmitter at the neuromuscular junction. J Cell Biol 110:449–459

    Article  PubMed  CAS  Google Scholar 

  50. Chi P, Greengard P, Ryan TA (2001) Synapsin dispersion and reclustering during synaptic activity. Nat Neurosci 4:1187–1193

    Article  PubMed  CAS  Google Scholar 

  51. Chi P, Greengard P, Ryan TA (2003) Synaptic vesicle mobilization is regulated by distinct synapsin I phosphorylation pathways at different frequencies. Neuron 38:69–78

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  53. 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 

  54. Takei Y, Harada A, Takeda S, Kobayashi K, Terada S, Noda T, Takahashi T, Hirokawa N (1995) Synapsin I deficiency results in the structural change in the presynaptic terminals in the murine nervous system. J Cell Biol 131:1789–1800

    Article  PubMed  CAS  Google Scholar 

  55. Ryan TA, Li L, Chin LS, Greengard P, Smith SJ (1996) Synaptic vesicle recycling in synapsin I knock-out mice. J Cell Biol 134:1219–1227

    Article  PubMed  CAS  Google Scholar 

  56. 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 

  57. 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 

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

    Article  PubMed  CAS  Google Scholar 

  59. Corradi A, Zanardi A, Giacomini C, Onofri F, Valtorta F, Zoli M, Benfenati F (2008) Synapsin-I- and synapsin-II-null mice display an increased age-dependent cognitive impairment. J Cell Sci 121:3042–3051

    Article  PubMed  CAS  Google Scholar 

  60. Samigullin D, Bill CA, Coleman WL, Bykhovskaia M (2004) Regulation of transmitter release by synapsin II in mouse motor terminals. J Physiol 561:149–158

    Article  PubMed  CAS  Google Scholar 

  61. Garcia CC, Blair HJ, Seager M, Coulthard A, Tennant S, Buddles M, Curtis A, Goodship JA (2004) Identification of a mutation in synapsin I, a synaptic vesicle protein, in a family with epilepsy. J Med Genet 41:183–186

    Article  PubMed  CAS  Google Scholar 

  62. Cavalleri GL, Weale ME, Shianna KV, Singh R, Lynch JM, Grinton B, Szoeke C, Murphy K, Kinirons P, O’Rourke D, Ge D, Depondt C, Claeys KG, Pandolfo M, Gumbs C, Walley N, McNamara J, Mulley JC, Linney KN, Sheffield LJ, Radtke RA, Tate SK, Chissoe SL, Gibson RA, Hosford D, Stanton A, Graves TD, Hanna MG, Eriksson K, Kantanen AM, Kalviainen R, O’Brien TJ, Sander JW, Duncan JS, Scheffer IE, Berkovic SF, Wood NW, Doherty CP, Delanty N, Sisodiya SM, Goldstein DB (2007) Multicentre search for genetic susceptibility loci in sporadic epilepsy syndrome and seizure types: a case-control study. Lancet Neurol 6:970–980

    Article  PubMed  CAS  Google Scholar 

  63. Fletcher TL, Cameron P, De Camilli P, Banker G (1991) The distribution of synapsin I and synaptophysin in hippocampal neurons developing in culture. J Neurosci 11:1617–1626

    PubMed  CAS  Google Scholar 

  64. Lu B, Greengard P, Poo MM (1992) Exogenous synapsin I promotes functional maturation of developing neuromuscular synapses. Neuron 8:521–529

    Article  PubMed  CAS  Google Scholar 

  65. Schaeffer E, Alder J, Greengard P, Poo MM (1994) Synapsin IIa accelerates functional development of neuromuscular synapses. Proc Natl Acad Sci USA 91:3882–3886

    Article  PubMed  CAS  Google Scholar 

  66. Dunia R, Herrera AA (1993) Synapse formation and elimination during growth of the pectoral muscle in Xenopus laevis. J Physiol 469:501–509

    PubMed  CAS  Google Scholar 

  67. Cash S, Zucker RS, Poo MM (1996) Spread of synaptic depression mediated by presynaptic cytoplasmic signalling. Science 272:998–1001

    Article  PubMed  CAS  Google Scholar 

  68. Han HQ, Greengard P (1994) Remodeling of cytoskeletal architecture of non-neuronal cells induced by synapsin. Proc Natl Acad Sci USA 91:8557–8561

    Article  PubMed  CAS  Google Scholar 

  69. Ferreira A, Kosik KS, Greengard P, Han HQ (1994) Aberrant neurites and synaptic vesicle protein deficiency in synapsin II-depleted neurons. Science 264:977–979

    Article  PubMed  CAS  Google Scholar 

  70. Ferreira A, Chin LS, Li L, Lanier LM, Kosik KS, Greengard P (1998) Distinct roles of synapsin I and synapsin II during neuronal development. Mol Med 4:22–28

    PubMed  CAS  Google Scholar 

  71. Ferreira A, Han HQ, 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 

  72. Ferreira A, Li L, Chin LS, Greengard P, Kosik KS (1996) Postsynaptic element contributes to the delay in synaptogenesis in synapsin I-deficient neurons. Mol Cell Neurosci 8:286–299

    Article  PubMed  CAS  Google Scholar 

  73. Kao HT, Song HJ, Porton B, Ming GL, Hoh J, Abraham M, Czernik AJ, Pieribone VA, Poo MM, Greengard P (2002) A protein kinase A-dependent molecular switch in synapsins regulates neurite outgrowth. Nat Neurosci 5:431–437

    PubMed  CAS  Google Scholar 

  74. Murrey HE, Gama CI, Kalovidouris SA, Luo WI, Driggers EM, Porton B, Hsieh-Wilson LC (2006) Protein fucosylation regulates synapsin Ia/Ib expression and neuronal morphology in primary hippocampal neurons. Proc Natl Acad Sci USA 103:21–26

    Article  PubMed  CAS  Google Scholar 

  75. Onofri F, Giovedi S, Vaccaro P, Czernik AJ, Valtorta F, De Camilli P, Greengard P, Benfenati F (1997) Synapsin I interacts with c-Src and stimulates its tyrosine kinase activity. Proc Natl Acad Sci USA 94:12168–12173

    Article  PubMed  CAS  Google Scholar 

  76. Tucker BA, Rahimtula M, Mearow KM (2008) Src and FAK are key early signalling intermediates required for neurite growth in NGF-responsive adult DRG neurons. Cell Signal 20:241–257

    Article  PubMed  CAS  Google Scholar 

  77. Han HQ, Nichols RA, Rubin MR, Bahler M, Greengard P (1991) Induction of formation of presynaptic terminals in neuroblastoma cells by synapsin IIb. Nature 349:697–700

    Article  PubMed  CAS  Google Scholar 

  78. Valtorta F, Iezzi N, Benfenati F, Lu B, Poo MM, Greengard P (1995) Accelerated structural maturation induced by synapsin I at developing neuromuscular synapses of Xenopus laevis. Eur J Neurosci 7:261–270

    Article  PubMed  CAS  Google Scholar 

  79. Giovedì S, Darchen F, Valtorta F, Greengard P, Benfenati F (2004) Synapsin is a novel Rab3 effector protein on small synaptic vesicles. II. Functional effects of the Rab3A-synapsin I interaction. J Biol Chem 279:43769–43779

    Article  PubMed  CAS  Google Scholar 

  80. Giovedì S, Vaccaro P, Valtorta F, Darchen F, Greengard P, Cesareni G, Benfenati F (2004) Synapsin is a novel Rab3 effector protein on small synaptic vesicles. I. Identification and characterization of the synapsin I-Rab3 interactions in vitro and in intact nerve terminals. J Biol Chem 279:43760–43768

    Article  PubMed  CAS  Google Scholar 

  81. Geppert M, Ullrich B, Green DG, Takei K, Daniels L, De Camilli P, Sudhof TC, Hammer RE (1994) Synaptic targeting domains of synapsin I revealed by transgenic expression in photoreceptor cells. EMBO J 13:3720–3727

    PubMed  CAS  Google Scholar 

  82. Gaffield MA, Betz WJ (2007) Synaptic vesicle mobility in mouse motor nerve terminals with and without synapsin. J Neurosci 27:13691–13700

    Article  PubMed  CAS  Google Scholar 

  83. Gitler D, Cheng Q, Greengard P, Augustine GJ (2008) Synapsin IIa controls the reserve pool of glutamatergic synaptic vesicles. J Neurosci 28:10835–10843

    Article  PubMed  CAS  Google Scholar 

  84. Godenschwege TA, Reisch D, Diegelmann S, Eberle K, Funk N, Heisenberg M, Hoppe V, Hoppe J, Klagges BR, Martin JR, Nikitina EA, Putz G, Reifegerste R, Reisch N, Rister J, Schaupp M, Scholz H, Schwarzel M, Werner U, Zars TD, Buchner S, Buchner E (2004) Flies lacking all synapsins are unexpectedly healthy but are impaired in complex behaviour. Eur J Neurosci 20:611–622

    Article  PubMed  Google Scholar 

  85. Ziv NE, Garner CC (2004) Cellular and molecular mechanisms of presynaptic assembly. Nat Rev Neurosci 5:385–399

    Article  PubMed  CAS  Google Scholar 

  86. Forscher P, Kaczmarek LK, Buchanan JA, Smith SJ (1987) Cyclic AMP induces changes in distribution and transport of organelles within growth cones of Aplysia bag cell neurons. J Neurosci 7:3600–3611

    PubMed  CAS  Google Scholar 

  87. Bonanomi D, Menegon A, Miccio A, Ferrari G, Corradi A, Kao HT, Benfenati F, Valtorta F (2005) Phosphorylation of synapsin I by cAMP-dependent protein kinase controls synaptic vesicle dynamics in developing neurons. J Neurosci 25:7299–7308

    Article  PubMed  CAS  Google Scholar 

  88. Sabo SL, Gomes RA, McAllister AK (2006) Formation of presynaptic terminals at predefined sites along axons. J Neurosci 26:10813–10825

    Article  PubMed  CAS  Google Scholar 

  89. Onofri F, Giovedi S, Kao HT, Valtorta F, Bongiorno Borbone L, De Camilli P, Greengard P, Benfenati F (2000) Specificity of the binding of synapsin I to Src homology 3 domains. J Biol Chem 275:29857–29867

    Article  PubMed  CAS  Google Scholar 

  90. Porton B, Kao HT, Greengard P (1999) Characterization of transcripts from the synapsin III gene locus. J Neurochem 73:2266–2271

    Article  PubMed  CAS  Google Scholar 

  91. Baldelli P, Fassio A, Corradi A, Cremona O, Valtorta F, Benfenati F (2005) Synapsins and neuroexocytosis: recent views from functional studies on synapsin null mutant mice. Arch Ital Biol 143:113–126

    PubMed  CAS  Google Scholar 

  92. Dotti CG, Sullivan CA, Banker GA (1988) The establishment of polarity by hippocampal neurons in culture. J Neurosci 8:1454–1468

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Drs. Paul Greengard (The Rockefeller University, New York, NY) and Hung-Teh Kao (Brown University, Providence, RI) for the long-standing collaboration in the synapsin field and for invaluable and stimulating discussions. This study was supported by research grants from the Italian Ministry of University and Research (PRIN and FIRB grants), the Compagnia di San Paolo-Torino, the Cariplo Foundation-Milano and the Mariani Foundation-Milano to F.B. and F.V. The support of Telethon-Italy (Grant GGP09134 to F.B. and F.V.) is also acknowledged.

Author information

Author notes

  1. Dario Bonanomi

    Present address: Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA, 92037, USA

Authors and Affiliations

  1. San Raffaele Scientific Institute, Vita-Salute University, Via Olgettina 58, 20132, Milan, Italy

    Eugenio F. Fornasiero, Dario Bonanomi & Flavia Valtorta

  2. Department of Neuroscience and Brain Technologies, The Italian Institute of Technology, Via Morego 30, 16163, Genoa, Italy

    Fabio Benfenati

  3. Department of Experimental Medicine, University of Genova, Viale Benedetto XV, 3, 16132, Genoa, Italy

    Fabio Benfenati

  4. Unit of Molecular Neuroscience, The Italian Institute of Technology, Via Olgettina 58, 20132, Milan, Italy

    Eugenio F. Fornasiero, Dario Bonanomi & Flavia Valtorta

Authors
  1. Eugenio F. Fornasiero
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dario Bonanomi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fabio Benfenati
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Flavia Valtorta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fabio Benfenati.

Additional information

F. Benfenati and F. Valtorta contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fornasiero, E.F., Bonanomi, D., Benfenati, F. et al. The role of synapsins in neuronal development. Cell. Mol. Life Sci. 67, 1383–1396 (2010). https://doi.org/10.1007/s00018-009-0227-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-009-0227-8

Keywords

Search

Navigation