The molecular architecture of the cytomatrix of presynaptic nerve terminals is poorly understood. Here we show that Bassoon, a novel protein of >400,000 Mr, is a new component of the presynaptic cytoskeleton. The murine bassoon gene maps to chromosome 9F. A comparison with the corresponding rat cDNA identified 10 exons within its protein-coding region. The Bassoon protein is predicted to contain two double-zinc fingers, several coiled-coil domains, and a stretch of polyglutamines (24 and 11 residues in rat and mouse, respectively). In some human proteins, e.g., Huntingtin, abnormal amplification of such poly-glutamine regions causes late-onset neurodegeneration. Bassoon is highly enriched in synaptic protein preparations. In cultured hippocampal neurons, Bassoon colocalizes with the synaptic vesicle protein synaptophysin and Piccolo, a presynaptic cytomatrix component. At the ultrastructural level, Bassoon is detected in axon terminals of hippocampal neurons where it is highly concentrated in the vicinity of the active zone. Immunogold labeling of synaptosomes revealed that Bassoon is associated with material interspersed between clear synaptic vesicles, and biochemical studies suggest a tight association with cytoskeletal structures. These data indicate that Bassoon is a strong candidate to be involved in cytomatrix organization at the site of neurotransmitter release.
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27 July 1998
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July 27 1998
Bassoon, a Novel Zinc-finger CAG/Glutamine-repeat Protein Selectively Localized at the Active Zone of Presynaptic Nerve Terminals
Susannetom Dieck,
Susannetom Dieck
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
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Lydia Sanmartí-Vila,
Lydia Sanmartí-Vila
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
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Kristina Langnaese,
Kristina Langnaese
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
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Karin Richter,
Karin Richter
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
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Stefan Kindler,
Stefan Kindler
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
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Antje Soyke,
Antje Soyke
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
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Heike Wex,
Heike Wex
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
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Karl-Heinz Smalla,
Karl-Heinz Smalla
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
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Udo Kämpf,
Udo Kämpf
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
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Jürgen-Theodor Fränzer,
Jürgen-Theodor Fränzer
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
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Markus Stumm,
Markus Stumm
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
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Craig C. Garner,
Craig C. Garner
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
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Eckart D. Gundelfinger
Eckart D. Gundelfinger
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
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Susannetom Dieck
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
Lydia Sanmartí-Vila
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
Kristina Langnaese
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
Karin Richter
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
Stefan Kindler
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
Antje Soyke
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
Heike Wex
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
Karl-Heinz Smalla
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
Udo Kämpf
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
Jürgen-Theodor Fränzer
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
Markus Stumm
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
Craig C. Garner
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
Eckart D. Gundelfinger
*Leibniz Institute for Neurobiology, D-39118 Magdeburg, Germany; ‡Institute for Cellular Biochemistry and Clinical Neurobiology, University of Hamburg, D-20246 Hamburg, Germany; §Institute for Human Genetics, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; ‖Institute for Pharmacology and Toxicology, Medical Faculty, Otto von Guericke University, D-39120 Magdeburg, Germany; and ¶Department of Neurobiology, University of Alabama at Birmingham, South Birmingham, Alabama 35213-0021
S. tom Dieck, L. Sanmartí-Vila, and K. Langnaese contributed equally to this work. The present address of Heike Wex is Department of Human Genetics, Mount Sinai School of Medicine, New York, NY 10029-6514.
Address all correspondence to Eckart D. Gundelfinger, Leibniz Institute for Neurobiology, Postfach 1860, D-39008 Magdeburg, Germany. Tel.: +49-391-6263-228; Fax: +49-391-6263-229; E-mail: [email protected]
2. It should be noted that Bassoon is a presynaptic protein that is highly enriched in the so-called PSD protein fraction. It has been shown previously that presynaptic proteins do occur in this fraction (Langnaese et al., 1996). Another well-documented example of this kind is the presynaptic cytomatrix component Piccolo (Cases-Langhoff et al., 1996). In a recent publication Ziff (1997) provides electron microscopic evidence for the appearence of presynaptic dense projections in the PSD preparation. This indicates that, though the PSD fraction indeed contains primarily postsynaptic proteins (Kennedy, 1997), the name of the fraction may be misleading. Therefore, we refer to this fraction as synaptic junctional protein preparation.
Received:
April 10 1998
Revision Received:
June 12 1998
Online ISSN: 1540-8140
Print ISSN: 0021-9525
1998
J Cell Biol (1998) 142 (2): 499–509.
Article history
Received:
April 10 1998
Revision Received:
June 12 1998
Citation
Susannetom Dieck, Lydia Sanmartí-Vila, Kristina Langnaese, Karin Richter, Stefan Kindler, Antje Soyke, Heike Wex, Karl-Heinz Smalla, Udo Kämpf, Jürgen-Theodor Fränzer, Markus Stumm, Craig C. Garner, Eckart D. Gundelfinger; Bassoon, a Novel Zinc-finger CAG/Glutamine-repeat Protein Selectively Localized at the Active Zone of Presynaptic Nerve Terminals . J Cell Biol 27 July 1998; 142 (2): 499–509. doi: https://doi.org/10.1083/jcb.142.2.499
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