Advertisement

Cell and Tissue Research

, Volume 326, Issue 2, pp 339–346 | Cite as

Ribbon synapses of the retina

  • Susanne tom Dieck
  • Johann Helmut Brandstätter
Review

Abstract

Vision is a highly complex task that involves several steps of parallel information processing in various areas of the central nervous system. Complex processing of visual signals occurs as early as at the retina, the first stage in the visual system. Various aspects of visual information are transmitted in parallel from the photoreceptors (the input neurons of the retina) through their interconnecting bipolar cells to the ganglion cells (the output neurons). Photoreceptors and bipolar cells transfer information via the release of the neurotransmitter glutamate at a specialized synapse, the ribbon synapse. Although known from early days of electron microscopy, the precise functioning of ribbon synapses has yet to be explained. In this review, we highlight recent advances towards understanding the molecular composition and function of this enigmatic synapse.

Keywords

Retina Ribbon synapse RIBEYE CtBP CAZ Active zone Mouse Zebrafish 

References

  1. Adly MA, Spiwoks-Becker I, Vollrath L (1999) Ultrastructural changes of photoreceptor synaptic ribbons in relation to time of day and illumination. Invest Ophthalmol Vis Sci 40:2165–2172PubMedGoogle Scholar
  2. Allwardt BA, Lall AB, Brockerhoff SE, Dowling JE (2001) Synapse formation is arrested in retinal photoreceptors of the zebrafish nrc mutant. J Neurosci 21:2330–2342PubMedGoogle Scholar
  3. Altrock WD, Dieck S tom, Sokolov M, Meyer AC, Sigler A, Brakebusch C, Fässler R, Richter K, Boeckers TM, Potschka H, Brandt C, Loscher W, Grimberg D, Dresbach T, Hempelmann A, Hassan H, Balschun D, Frey JU, Brandstätter JH, Garner CC, Rosenmund C, Gundelfinger ED (2003) Functional inactivation of a fraction of excitatory synapses in mice deficient for the active zone protein Bassoon. Neuron 37:787–800PubMedCrossRefGoogle Scholar
  4. Ball SL, Powers PA, Shin HS, Morgans CW, Peachey NS, Gregg RG (2002) Role of the β2 subunit of voltage-dependent calcium channels in the retinal outer plexiform layer. Invest Ophthalmol Vis Sci 43:1595–1603PubMedGoogle Scholar
  5. Bech-Hansen NT, Naylor MJ, Maybaum TA, Pearce WG, Koop B, Fishman GA, Mets M, Musarella MA, Boycott KM (1998) Loss-of-function mutations in a calcium-channel α1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness. Nat Genet 19:264–267PubMedCrossRefGoogle Scholar
  6. Bonazzi M, Spano S, Turacchio G, Cericola C, Valente C, Colanzi A, Kweon HS, Hsu VW, Polishchuck EV, Polishchuck RS, Sallese M, Pulvirenti T, Corda D, Luini A (2005) CtBP3/BARS drives membrane fission in dynamin-independent transport pathways. Nat Cell Biol 7:570–580PubMedCrossRefGoogle Scholar
  7. Brandstätter JH, Fletcher EL, Garner CC, Gundelfinger ED, Wässle H (1999) Differential expression of the presynaptic cytomatrix protein Bassoon among ribbon synapses in the mammalian retina. Eur J Neurosci 11:3683–3693PubMedCrossRefGoogle Scholar
  8. Brockerhoff SE, Hurley JB, Janssen-Bienhold U, Neuhauss SC, Driever W, Dowling JE (1995) A behavioral screen for isolating zebrafish mutants with visual system defects. Proc Natl Acad Sci USA 92:10545–10549PubMedCrossRefGoogle Scholar
  9. Brose N, Hofmann K, Hata Y, Südhof TC (1995) Mammalian homologues of Caenorhabditis elegans unc-13 gene define novel family of C2-domain proteins. J Biol Chem 270:25273–25280PubMedCrossRefGoogle Scholar
  10. Calakos N, Schoch S, Südhof TC, Malenka RC (2004) Multiple roles for the active zone protein RIM1α in late stages of neurotransmitter release. Neuron 42:889–896PubMedCrossRefGoogle Scholar
  11. Chang B, Heckenlively JR, Bayley PR, Brecha NC, Davisson MT, Hawes NL, Hirano AA, Hurd RE, Ikeda A, Johnson BA, McCall MA, Morgans CW, Nusinowitz S, Peachey NS, Rice DS, Vessey KA, Gregg RG (2006) The nob2 mouse, a null mutation in Cacna1f: anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses. Vis Neurosci 23:11–24PubMedCrossRefGoogle Scholar
  12. Deguchi-Tawarada M, Inoue E, Takao-Rikitsu E, Inoue M, Kitajima I, Ohtsuka T, Takai Y (2006) Active zone protein CAST is a component of conventional and ribbon synapses in mouse retina. J Comp Neurol 495:480–496PubMedCrossRefGoogle Scholar
  13. Dick O, Hack I, Altrock WD, Garner CC, Gundelfinger ED, Brandstätter JH (2001) Localization of the presynaptic cytomatrix protein Piccolo at ribbon and conventional synapses in the rat retina: comparison with Bassoon. J Comp Neurol 439:224–234PubMedCrossRefGoogle Scholar
  14. Dick O, tom Dieck S, Altrock WD, Ammermüller J, Weiler R, Garner CC, Gundelfinger ED, Brandstätter JH (2003) The presynaptic active zone protein Bassoon is essential for photoreceptor ribbon synapse formation in the retina. Neuron 37:775–786PubMedCrossRefGoogle Scholar
  15. Dieck S tom, Sanmarti-Vila L, Langnaese K, Richter K, Kindler S, Soyke A, Wex H, Smalla KH, Kampf U, Franzer JT, Stumm M, Garner CC, Gundelfinger ED (1998) Bassoon, a novel zinc-finger CAG/glutamine-repeat protein selectively localized at the active zone of presynaptic nerve terminals. J Cell Biol 142:499–509CrossRefGoogle Scholar
  16. Dieck S tom, Altrock WD, Kessels MM, Qualmann B, Regus H, Brauner D, Fejtova A, Bracko O, Gundelfinger ED, Brandstätter JH (2005) Molecular dissection of the photoreceptor ribbon synapse: physical interaction of Bassoon and RIBEYE is essential for the assembly of the ribbon complex. J Cell Biol 168:825–836CrossRefGoogle Scholar
  17. Dieck S tom, Schmitz F, Brandstätter JH (2006) CtBPs as synaptic proteins. In: Chinnadurai G (ed) CtBP family proteins. Landes Bioscience, Georgetown (in press)Google Scholar
  18. Dowling JE (1987) The retina: an approachable part of the brain. Harvard University Press, Cambridge, MassGoogle Scholar
  19. Fuchs PA, Glowatzki E, Moser T (2003) The afferent synapse of cochlear hair cells. Curr Opin Neurobiol 13:452–458PubMedCrossRefGoogle Scholar
  20. Gallop JL, Butler PJ, McMahon HT (2005) Endophilin and CtBP/BARS are not acyl transferases in endocytosis or Golgi fission. Nature 438:675–678PubMedCrossRefGoogle Scholar
  21. Gersdorff H von (2001) Synaptic ribbons: versatile signal transducers. Neuron 29:7–10CrossRefGoogle Scholar
  22. Gersdorff H von, Vardi E, Matthews G, Sterling P (1996) Evidence that vesicles on the synaptic ribbon of retinal bipolar neurons can be rapidly released. Neuron 16:1221–1227CrossRefGoogle Scholar
  23. Gregg RG, Mukhopadhyay S, Candille SI, Ball SL, Pardue MT, McCall MA, Peachey NS (2003) Identification of the gene and the mutation responsible for the mouse nob phenotype. Invest Ophthalmol Vis Sci 44:378–384PubMedCrossRefGoogle Scholar
  24. Haeseleer F, Imanishi Y, Maeda T, Possin DE, Maeda A, Lee A, Rieke F, Palczewski K (2004) Essential role of Ca2+-binding protein 4, a Cav1.4 channel regulator, in photoreceptor synaptic function. Nat Neurosci 7:1079–1087PubMedCrossRefGoogle Scholar
  25. Heidelberger R, Heinemann C, Neher E, Matthews G (1994) Calcium dependence of the rate of exocytosis in a synaptic terminal. Nature 371:513–515PubMedCrossRefGoogle Scholar
  26. Heidelberger R, Sterling P, Matthews G (2002) Roles of ATP in depletion and replenishment of the releasable pool of synaptic vesicles. J Neurophysiol 88:98–106PubMedCrossRefGoogle Scholar
  27. Heidelberger R, Wang MM, Sherry DM (2003) Differential distribution of synaptotagmin immunoreactivity among synapses in the goldfish, salamander, and mouse retina. Vis Neurosci 20:37–49PubMedCrossRefGoogle Scholar
  28. Heidelberger R, Thoreson WB, Witkovsky P (2005) Synaptic transmission at retinal ribbon synapses. Prog Retin Eye Res 24:682–720PubMedCrossRefGoogle Scholar
  29. Hidalgo Carcedo C, Bonazzi M, Spano S, Turacchio G, Colanzi A, Luini A, Corda D (2004) Mitotic Golgi partitioning is driven by the membrane-fissioning protein CtBP3/BARS. Science 305:93–96PubMedCrossRefGoogle Scholar
  30. Hildebrand JD, Soriano P (2002) Overlapping and unique roles for C-terminal binding protein 1 (CtBP1) and CtBP2 during mouse development. Mol Cell Biol 22:5296–5307PubMedCrossRefGoogle Scholar
  31. Holt M, Cooke A, Neef A, Lagnado L (2004) High mobility of vesicles supports continuous exocytosis at a ribbon synapse. Curr Biol 14:173–183PubMedGoogle Scholar
  32. Hosoya O, Tsutsui K, Tsutsui K (2004) Localized expression of amphiphysin Ir, a retina-specific variant of amphiphysin I, in the ribbon synapse and its functional implication. Eur J Neurosci 19:2179–2187PubMedCrossRefGoogle Scholar
  33. Khimich D, Nouvian R, Pujol R, tom Dieck S, Egner A, Gundelfinger ED, Moser T (2005) Hair cell synaptic ribbons are essential for synchronous auditory signalling. Nature 434:889–894PubMedCrossRefGoogle Scholar
  34. Lenzi D, Gersdorff H von (2001) Structure suggests function: the case for synaptic ribbons as exocytotic nanomachines. Bioessays 23:831–840PubMedCrossRefGoogle Scholar
  35. Libby RT, Lavallee CR, Balkema GW, Brunken WJ, Hunter DD (1999) Disruption of laminin β2 chain production causes alterations in morphology and function in the CNS. J Neurosci 19:9399–9411PubMedGoogle Scholar
  36. Libby RT, Lillo C, Kitamoto J, Williams DS, Steel KP (2004) Myosin Va is required for normal photoreceptor synaptic activity. J Cell Sci 117:4509–4515PubMedCrossRefGoogle Scholar
  37. Mandell JW, Townes-Anderson E, Czernik AJ, Cameron R, Greengard P, De Camilli P (1990) Synapsins in the vertebrate retina: absence from ribbon synapses and heterogeneous distribution among conventional synapses. Neuron 5:19–33PubMedCrossRefGoogle Scholar
  38. Mandell JW, Czernik AJ, De Camilli P, Greengard P, Townes-Anderson E (1992) Differential expression of synapsins I and II among rat retinal synapses. J Neurosci 12:1736–1749PubMedGoogle Scholar
  39. Mansergh F, Orton NC, Vessey JP, Lalonde MR, Stell WK, Tremblay F, Barnes S, Rancourt DE, Bech-Hansen NT (2005) Mutation of the calcium channel gene Cacna1f disrupts calcium signaling, synaptic transmission and cellular organization in mouse retina. Hum Mol Genet 14:3035–3046PubMedCrossRefGoogle Scholar
  40. Masu M, Iwakabe H, Tagawa Y, Miyoshi T, Yamashita M, Fukuda Y, Sasaki H, Hiroi K, Nakamura Y, Shigemoto R, Takada M, Nakamura K, Nakao K, Katsuki M, Nakanishi S (1995) Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene. Cell 80:757–765PubMedCrossRefGoogle Scholar
  41. Michaelides M, Holder GE, Hunt DM, Fitzke FW, Bird AC, Moore AT (2005) A detailed study of the phenotype of an autosomal dominant cone-rod dystrophy (CORD7) associated with mutation in the gene for RIM1. Br J Ophthalmol 89:198–206PubMedCrossRefGoogle Scholar
  42. Morgans CW (2001) Localization of the α1F calcium channel subunit in the rat retina. Invest Ophthalmol Vis Sci 42:2414–2418PubMedGoogle Scholar
  43. Morgans CW, Brandstätter JH, Kellerman J, Betz H, Wässle H (1996) A SNARE complex containing syntaxin 3 is present in ribbon synapses of the retina. J Neurosci 16:6713–6721PubMedGoogle Scholar
  44. Muresan V, Lyass A, Schnapp BJ (1999) The kinesin motor KIF3A is a component of the presynaptic ribbon in vertebrate photoreceptors. J Neurosci 19:1027–1037PubMedGoogle Scholar
  45. Ohtsuka T, Takao-Rikitsu E, Inoue E, Inoue M, Takeuchi M, Matsubara K, Deguchi-Tawarada M, Satoh K, Morimoto K, Nakanishi H, Takai Y (2002) CAST: a novel protein of the cytomatrix at the active zone of synapses that forms a ternary complex with RIM1 and Munc13-1. J Cell Biol 158:577–590PubMedCrossRefGoogle Scholar
  46. Parsons TD, Sterling P (2003) Synaptic ribbon: conveyor belt or safety belt? Neuron 37:379–382PubMedCrossRefGoogle Scholar
  47. Pieribone VA, Shupliakov O, Brodin L, Hilfiker-Rothenfluh S, Czernik AJ, Greengard P (1995) Distinct pools of synaptic vesicles in neurotransmitter release. Nature 375:493–497PubMedCrossRefGoogle Scholar
  48. Rabl K, Cadetti L, Thoreson WB (2005) Kinetics of exocytosis is faster in cones than in rods. J Neurosci 25:4633–4640PubMedCrossRefGoogle Scholar
  49. Rao-Mirotznik R, Harkins AB, Buchsbaum G, Sterling P (1995) Mammalian rod terminal: architecture of a binary synapse. Neuron 14:561–569PubMedCrossRefGoogle Scholar
  50. Rea R, Li J, Dharia A, Levitan ES, Sterling P, Kramer RH (2004) Streamlined synaptic vesicle cycle in cone photoreceptor terminals. Neuron 41:755–766PubMedCrossRefGoogle Scholar
  51. Reim K, Wegmeyer H, Brandstätter JH, Xue M, Rosenmund C, Dresbach T, Hofmann K, Brose N (2005) Structurally and functionally unique complexins at retinal ribbon synapses. J Cell Biol 169:669–680PubMedCrossRefGoogle Scholar
  52. Richter K, Langnaese K, Kreutz MR, Olias G, Zhai R, Scheich H, Garner CC, Gundelfinger ED (1999) Presynaptic cytomatrix protein Bassoon is localized at both excitatory and inhibitory synapses of rat brain. J Comp Neurol 408:437–448PubMedCrossRefGoogle Scholar
  53. Rosahl TW, Geppert M, Spillane D, Herz J, Hammer RE, Malenka RC, Südhof TC (1995) Short-term synaptic plasticity is altered in mice lacking synapsin I. Cell 75:661–670CrossRefGoogle Scholar
  54. Rosenmund C, Rettig J, Brose N (2003) Molecular mechanisms of active zone function. Curr Opin Neurobiol 13:509–519PubMedCrossRefGoogle Scholar
  55. Ruether K, Apfelstedt-Sylla E, Zrenner E (1993) Clinical findings in patients with congenital stationary night blindness of the Schubert-Bornschein type. German J Ophthalmol 2:429–435Google Scholar
  56. Saviane C, Silver RA (2006) Fast vesicle reloading and a large pool sustain high bandwidth transmission at a central synapse. Nature 439:983–987PubMedCrossRefGoogle Scholar
  57. Schlamp CL, Williams DS (1996) Myosin V in the retina: localization in the rod photoreceptor synapse. Exp Eye Res 63:613–619PubMedCrossRefGoogle Scholar
  58. Schmitz F, Drenckhahn D (1993) Li+-induced structural changes of synaptic ribbons are related to the phosphoinositide metabolism in photoreceptor synapses. Brain Res 604:142–148PubMedCrossRefGoogle Scholar
  59. Schmitz F, Königstorfer A, Südhof TC (2000) RIBEYE, a component of synaptic ribbons: a protein’s journey through evolution provides insight into synaptic ribbon function. Neuron 28:857–872PubMedCrossRefGoogle Scholar
  60. Schoch S, Castillo PE, Jo T, Mukherjee K, Geppert M, Wang Y, Schmitz F, Malenka RC, Südhof TC (2002) RIM1α forms a protein scaffold for regulating neurotransmitter release at the active zone. Nature 415:321–326PubMedCrossRefGoogle Scholar
  61. Spiwoks-Becker I, Glas M, Lasarzik I, Vollrath L (2004) Mouse photoreceptor synaptic ribbons lose and regain material in response to illumination changes. Eur J Neurosci 19:1559–1571PubMedCrossRefGoogle Scholar
  62. Sterling P, Matthews G (2005) Structure and function of ribbon synapses. Trends Neurosci 28:20–29PubMedCrossRefGoogle Scholar
  63. Stevens CF, Tsujimoto T (1995) Estimates for the pool size of releasable quanta at a single central synapse and for the time required to refill the pool. Proc Natl Acad Sci USA 92:846–849PubMedCrossRefGoogle Scholar
  64. Strom TM, Nyakatura G, Apfelstedt-Sylla E, Hellebrand H, Lorenz B, Weber BHF, Wutz K, Gutwillinger N, Rüther K, Drescher B, Sauer C, Zrenner E, Meitinger T, Rosenthal A, Meindl A (1998) An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness. Nat Genet 19:260–263PubMedCrossRefGoogle Scholar
  65. Südhof TC (2004) The synaptic vesicle cycle. Annu Rev Neurosci 27:509–547PubMedCrossRefGoogle Scholar
  66. Takao-Rikitsu E, Mochida S, Inoue E, Deguchi-Tawarada M, Inoue M, Ohtsuka T, Takai Y (2004) Physical and functional interaction of the active zone proteins, CAST, RIM1, and Bassoon, in neurotransmitter release. J Cell Biol 164:301–311PubMedCrossRefGoogle Scholar
  67. Van Epps HA, Hayashi M, Lucast L, Stearns GW, Hurley JB, DeCamilli P, Brockerhoff SE (2004) The zebrafish nrc mutant reveals a role for the polyphosphoinositide phosphatase synaptojanin 1 in cone photoreceptor ribbon anchoring. J Neurosci 24:8641–8650PubMedCrossRefGoogle Scholar
  68. Wan L, Almers W, Chen W (2005) Two ribeye genes in teleosts: the role of Ribeye in ribbon formation and bipolar cell development. J Neurosci 25:941–949PubMedCrossRefGoogle Scholar
  69. Wang Y, Okamoto M, Schmitz F, Hofmann K, Südhof TC (1997) Rim is a putative Rab3 effector in regulating synaptic-vesicle fusion. Nature 388:593–598PubMedCrossRefGoogle Scholar
  70. Wässle H (2004) Parallel processing in the mammalian retina. Nat Rev 5:1–11Google Scholar
  71. Weigert R, Silletta MG, Spano S, Turacchio G, Cericola C, Colanzi A, Senatore S, Mancini R, Polishchuk EV, Salmona M, Facchiano F, Burger KN, Mironov A, Luini A, Corda D (1999) CtBP/BARS induces fission of Golgi membranes by acylating lysophosphatidic acid. Nature 402:429–433PubMedCrossRefGoogle Scholar
  72. Zenisek D, Horst NK, Merrifield C, Sterling P, Matthews G (2004) Visualizing synaptic ribbons in the living cell. J Neurosci 24:9752–9759PubMedCrossRefGoogle Scholar
  73. Zhai RG, Bellen HJ (2004) The architecture of the active zone in the presynaptic nerve terminal. Physiology 19:262–270PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Susanne tom Dieck
    • 1
    • 2
  • Johann Helmut Brandstätter
    • 1
    • 2
  1. 1.Institute for Biology, Department of ZoologyUniversity of Erlangen-NuernbergErlangenGermany
  2. 2.Department of NeuroanatomyMax Planck Institute for Brain ResearchFrankfurt/MainGermany

Personalised recommendations