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 Chemical Synapses (AG Gundelfinger)

 Molecular organization and assembly of the active zone of neurotransmitter release

At the ultra-structural level, the Cytomatrix assembled at the Active Zone is visible as a presynaptic dense projection. The identification of two integral components of the CAZ, i.e. the giant proteins Bassoon and Piccolo, has paved the way to study the molecular organization of the CAZ. Bassoon and Piccolo are thought to be members of the ensemble of proteins orchestrating the events at the active zone ( Fig. 6 ). The two proteins appear very early during synaptogenesis at sites of actively cycling synaptic vesicles and are prominent components of active zone precursor vesicles, large particles of pre-assembled active zones (Fig. 7).

 Molecular organization of the CAZ. The CAZ-specific multi-domain proteins RIMs, Bassoon and Piccolo and the CAST/ERC proteins are thought to act as major scaffolding proteins of the presynaptic cytomatrix. They can recruit a variety of effector proteins to the CAZ and thereby organize presynaptic processes functionally and topologically. The CAZ-specific protein Munc13 serves as a priming factor for synaptic vesicles.

Figure 6: Molecular organization of the CAZ. The CAZ-specific multi-domain proteins RIMs, Bassoon and Piccolo and the CAST/ERC proteins are thought to act as major scaffolding proteins of the presynaptic cytomatrix. They can recruit a variety of effector proteins to the CAZ and thereby organize presynaptic processes functionally and topologically. The CAZ-specific protein Munc13 serves as a priming factor for synaptic vesicles.

The active zone transport vesicle hypothesis. A tight collaboration with the labs of Craig Garner, Stanford, and Noam Ziv, Haifa, led us to propose to the hypothesis that during brain development active zones are assembled inside the neuron. Then they are transported along axons on so-called Piccolo-Bassoon transport vesicles (PTVs) to the site of synaptogenesis where they can fuse with the presynaptic plasma membrane.

Figure 7: The active zone transport vesicle hypothesis. A tight collaboration with the labs of Craig Garner, Stanford, and Noam Ziv, Haifa, led us to propose to the hypothesis that during brain development active zones are assembled inside the neuron. Then they are transported along axons on so-called Piccolo-Bassoon transport vesicles (PTVs) to the site of synaptogenesis where they can fuse with the presynaptic plasma membrane.

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Collaborators in the project:

  • Wilko Altrock
  • Ferdinand Bischof
  • Dasha Davydova (DFG GRK)
  • Anna Fejtova (SynScaff)
  • Bettina Kracht
  • Vesna Lazarevic (LSA N2)
  • Britta Qualmann
  • Michael Kessels

External collaborations:

Selected publications:

Dresbach T, Torres V, Wittenmayer N, Altrock WD, Zamorano P, Zuschratter W, Nawrotzki R, Ziv NE, Garner CC, Gundelfinger ED (2006) Assembly of Active Zone Precursor Vesicles: OBLIGATORY TRAFFICKING OF PRESYNAPTIC CYTOMATRIX PROTEINS BASSOON AND PICCOLO VIA A TRANS-GOLGI COMPARTMENT. J Biol Chem 281(9):6038-6047.[Link]

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(7035):889-894.[Link]

tom Dieck S, Altrock WD, Kessels MM, Qualmann B, Regus H, Brauner D, Fejtova A, Bracko O, Gundelfinger ED, Brandstatter 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(5):825-836.[Link]

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(6):1507-1520.[Link]

Dick O, tom Dieck S, Altrock WD, Ammermuller J, Weiler R, Garner CC, Gundelfinger ED, Brandstaetter JH (2003) The presynaptic active zone protein bassoon is essential for photoreceptor ribbon synapse formation in the retina. Neuron 37(5):775-786.[Link]

Dresbach T, Altrock WD, Gundelfinger ED (2003) Neurotransmitterfreisetzung an chemischen Synapsen: Zusammenbau und molekulare Organisation der aktiven Zone. Neuroforum 3/03.[Link]

Dresbach T, Hempelmann A, Spilker C, tom Dieck S, Altrock WD, Zuschratter W, Garner CC, Gundelfinger ED (2003) Functional regions of the presynaptic cytomatrix protein bassoon: significance for synaptic targeting and cytomatrix anchoring. Mol Cell Neurosci 23(2):279-291.[Link]

Fenster SD, Kessels MM, Qualmann B, Chung WJ, Nash J, Gundelfinger ED, Garner CC (2003) Interactions between Piccolo and the actin/dynamin-binding protein Abp1 link vesicle endocytosis to presynaptic active zones. J Biol Chem 278(22):20268-20277.[Link]

Gundelfinger ED, Kessels MM, Qualmann B (2003) Temporal and spatial coordination of exocytosis and endocytosis. Nat Rev Mol Cell Biol 4(2):127-139.[Link]

Kim S, Ko J, Shin H, Lee JR, Lim C, Han JH, Altrock WD, Garner CC, Gundelfinger ED, Premont RT, Kaang BK, Kim E (2003) The GIT family of proteins forms multimers and associates with the presynaptic cytomatrix protein Piccolo. J Biol Chem 278(8):6291-6300.[Link]

Shapira M, Zhai RG, Dresbach T, Bresler T, Torres VI, Gundelfinger ED, Ziv NE, Garner CC (2003) Unitary assembly of presynaptic active zones from Piccolo-Bassoon transport vesicles. Neuron 38(2):237-252.[Link]

Garner CC, Zhai RG, Gundelfinger ED, Ziv NE (2002) Molecular mechanisms of CNS synaptogenesis. Trends Neurosci 25(5):243-251.

Dick O, Hack I, Altrock WD, Garner CC, Gundelfinger ED, Brandstatter 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(2):224-234.[Link]

Dresbach T, Qualmann B, Kessels MM, Garner CC, Gundelfinger ED (2001) The presynaptic cytomatrix of brain synapses. Cell Mol Life Sci 58(1):94-116.

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(1):131-143.[Link]

Fenster SD, Chung WJ, Zhai R, Cases-Langhoff C, Voss B, Garner AM, Kaempf U, Kindler S, Gundelfinger ED, Garner CC (2000) Piccolo, a presynaptic zinc finger protein structurally related to bassoon. Neuron 25(1):203-214.[Link]

Garner CC, Kindler S, Gundelfinger ED (2000) Molecular determinants of presynaptic active zones. Curr Opin Neurobiol 10(3):321-327.

Gundelfinger ED, tom Dieck S (2000) Molecular organization of excitatory chemical synapses in the mammalian brain. Naturwissenschaften 87(12):513-523.

Sanmart?-Vila L, tom Dieck S, Richter K, Altrock W, Zhang L, Volknandt W, Zimmermann H, Garner CC, Gundelfinger ED, Dresbach T (2000) Membrane-association of presynaptic cytomatrix protein bassoon. Biochem Biophys Res Commun 275(1):43-46.

Zhai R, Olias G, Chung WJ, Lester RA, tom Dieck S, Langnaese K, Kreutz MR, Kindler S, Gundelfinger ED, Garner CC (2000) Temporal appearance of the presynaptic cytomatrix protein bassoon during synaptogenesis. Mol Cell Neurosci 15(5):417-428.

Zhang L, Volknandt W, Gundelfinger ED, Zimmermann H (2000) A comparison of synaptic protein localization in hippocampal mossy fiber terminals and neurosecretory endings of the neurohypophysis using the cryo-immunogold technique. J Neurocytol 29(1):19-30.

Brandstaetter JH, Fletcher EL, Garner CC, Gundelfinger ED, Waessle H (1999) Differential expression of the presynaptic cytomatrix protein bassoon among ribbon synapses in the mammalian retina. Eur J Neurosci 11(10):3683-3693.

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(3):437-448.[Link]

Winter C, tom Dieck S, Boeckers TM, Bockmann J, Kampf U, Sanmarti-Vila L, Langnaese K, Altrock W, Stumm M, Soyke A, Wieacker P, Garner CC, Gundelfinger ED (1999) The presynaptic cytomatrix protein Bassoon: sequence and chromosomal localization of the human BSN gene. Genomics 57(3):389-397.[Link]

tom Dieck S, Sanmart?-Vila L, Langnaese K, Richter K, Kindler S, Soyke A, Wex H, Smalla KH, Kaempf U, Fraenzer J-T, 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(2):499-509.

Cases-Langhoff C, Voss B, Garner AM, Appeltauer U, Takei K, Kindler S, Veh RW, De Camilli P, Gundelfinger ED, Garner CC (1996) Piccolo, a novel 420 kDa protein associated with the presynaptic cytomatrix. Eur J Cell Biol 69(3):214-223.

Garner CC, Garner A, Voss B, Appeltauer U, Gundelfinger ED (1993) Identifying novel synapse-associated proteins. In: Neuronal Cytoskeleton - Morphogenesis, Transport and Synaptic Transmission (Hirokawa N, ed), pp 317-329. London, UK: Japan Scientific Societies Press, CRC Press.[Link]

found 27 datasets

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