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Native GABAB receptors are heteromultimers with a family of auxiliary subunits

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  • Jochen Schwenk

    (Institute of Physiology II, University of Freiburg, Engesserstrasse 4, 79108 Freiburg, Germany)

  • Michaela Metz

    (Institute of Physiology, Pharmazentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland)

  • Gerd Zolles

    (Institute of Physiology II, University of Freiburg, Engesserstrasse 4, 79108 Freiburg, Germany)

  • Rostislav Turecek

    (Institute of Physiology, Pharmazentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland
    Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 14220-Prague 4, Czech Republic)

  • Thorsten Fritzius

    (Institute of Physiology, Pharmazentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland)

  • Wolfgang Bildl

    (Institute of Physiology II, University of Freiburg, Engesserstrasse 4, 79108 Freiburg, Germany)

  • Etsuko Tarusawa

    (Institute of Anatomy and Cell Biology, University of Freiburg, Albertstrasse 23, 79104 Freiburg, Germany)

  • Akos Kulik

    (Institute of Anatomy and Cell Biology, University of Freiburg, Albertstrasse 23, 79104 Freiburg, Germany)

  • Andreas Unger

    (Institute of Anatomy and Cell Biology, University of Freiburg, Albertstrasse 23, 79104 Freiburg, Germany)

  • Klara Ivankova

    (Institute of Physiology, Pharmazentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland)

  • Riad Seddik

    (Institute of Physiology, Pharmazentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland)

  • Jim Y. Tiao

    (Institute of Physiology, Pharmazentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland)

  • Mathieu Rajalu

    (Institute of Physiology, Pharmazentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland)

  • Johana Trojanova

    (Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 14220-Prague 4, Czech Republic)

  • Volker Rohde

    (Logopharm GmbH, Engesserstrasse 4, 79108 Freiburg, Germany)

  • Martin Gassmann

    (Institute of Physiology, Pharmazentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland)

  • Uwe Schulte

    (Institute of Physiology II, University of Freiburg, Engesserstrasse 4, 79108 Freiburg, Germany
    Logopharm GmbH, Engesserstrasse 4, 79108 Freiburg, Germany)

  • Bernd Fakler

    (Institute of Physiology II, University of Freiburg, Engesserstrasse 4, 79108 Freiburg, Germany
    Center for Biological Signaling Studies (bioss), Albertstrasse 10, 79104 Freiburg, Germany)

  • Bernhard Bettler

    (Institute of Physiology, Pharmazentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland)

Abstract

GABAB receptor helpers A proteomics study of GABAB receptors, the receptors for γ-aminobutyric acid, the main inhibitory neurotransmitter in the brain, throws new light on the origin of their functional diversity. Rather than being heterodimers of the well-known GABAB1 and GABAB2 subunits, GABAB receptors are shown to be high-molecular-weight complexes of GABAB1, GABAB2 and four sequence-related members of the KCTD (potassium channel tetramerization domain-containing) family of proteins. The KCTD proteins increase agonist potency and markedly alter the G-protein signalling of the receptors, suggesting that these proteins act as auxiliary subunits of GABAB receptors, determining the pharmacology and kinetics of the receptor response.

Suggested Citation

  • Jochen Schwenk & Michaela Metz & Gerd Zolles & Rostislav Turecek & Thorsten Fritzius & Wolfgang Bildl & Etsuko Tarusawa & Akos Kulik & Andreas Unger & Klara Ivankova & Riad Seddik & Jim Y. Tiao & Math, 2010. "Native GABAB receptors are heteromultimers with a family of auxiliary subunits," Nature, Nature, vol. 465(7295), pages 231-235, May.
    • Handle: RePEc:nat:nature:v:465:y:2010:i:7295:d:10.1038_nature08964
    DOI: 10.1038/nature08964
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    Cited by:

    1. Maciej K. Kocylowski & Hande Aypek & Wolfgang Bildl & Martin Helmstädter & Philipp Trachte & Bernhard Dumoulin & Sina Wittösch & Lukas Kühne & Ute Aukschun & Carolin Teetzen & Oliver Kretz & Botond Ga, 2022. "A slit-diaphragm-associated protein network for dynamic control of renal filtration," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Chanjuan Xu & Yiwei Zhou & Yuxuan Liu & Li Lin & Peng Liu & Xiaomei Wang & Zhengyuan Xu & Jean-Philippe Pin & Philippe Rondard & Jianfeng Liu, 2024. "Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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