Native GABAB receptors are heteromultimers with a family of auxiliary subunits

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, Mathieu Rajalu, Johana Trojanova, Volker Rohde, Martin Gassmann, Uwe Schulte, Bernd Fakler () and Bernhard Bettler ()
Additional contact information
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
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
Bernd Fakler: Institute of Physiology II, University of Freiburg, Engesserstrasse 4, 79108 Freiburg, Germany
Bernhard Bettler: Institute of Physiology, Pharmazentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland

Nature, 2010, vol. 465, issue 7295, 231-235

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.

Date: 2010
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DOI: 10.1038/nature08964

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