Journal article
Modular composition and dynamics of native GABAB receptors identified by high-resolution proteomics.
- Schwenk J Institute of Physiology, University of Freiburg, Freiburg, Germany.
- Pérez-Garci E Department of Biomedicine, Institute of Physiology, Pharmazentrum, University of Basel, Basel, Switzerland.
- Schneider A Institute of Physiology, University of Freiburg, Freiburg, Germany.
- Kollewe A Institute of Physiology, University of Freiburg, Freiburg, Germany.
- Gauthier-Kemper A Department of Cellular Biophysics, Institute of Medical Physics and Biophysics, University of Münster, Münster, Germany.
- Fritzius T Department of Biomedicine, Institute of Physiology, Pharmazentrum, University of Basel, Basel, Switzerland.
- Raveh A Department of Biomedicine, Institute of Physiology, Pharmazentrum, University of Basel, Basel, Switzerland.
- Dinamarca MC Department of Biomedicine, Institute of Physiology, Pharmazentrum, University of Basel, Basel, Switzerland.
- Hanuschkin A Optophysiology Lab, Department of Biology, University of Freiburg, Freiburg, Germany.
- Bildl W Institute of Physiology, University of Freiburg, Freiburg, Germany.
- Klingauf J Department of Cellular Biophysics, Institute of Medical Physics and Biophysics, University of Münster, Münster, Germany.
- Gassmann M Department of Biomedicine, Institute of Physiology, Pharmazentrum, University of Basel, Basel, Switzerland.
- Schulte U Institute of Physiology, University of Freiburg, Freiburg, Germany.
- Bettler B Department of Biomedicine, Institute of Physiology, Pharmazentrum, University of Basel, Basel, Switzerland.
- Fakler B Institute of Physiology, University of Freiburg, Freiburg, Germany.
- 2015-12-23
Published in:
- Nature neuroscience. - 2016
Amyloid beta-Protein Precursor
Animals
Caveolin 2
Cell Membrane
Epitopes
Mice
Mice, Inbred BALB C
Mice, Knockout
Proteomics
Rats
Rats, Wistar
Receptors, G-Protein-Coupled
Receptors, GABA-B
Signal Transduction
English
GABAB receptors, the most abundant inhibitory G protein-coupled receptors in the mammalian brain, display pronounced diversity in functional properties, cellular signaling and subcellular distribution. We used high-resolution functional proteomics to identify the building blocks of these receptors in the rodent brain. Our analyses revealed that native GABAB receptors are macromolecular complexes with defined architecture, but marked diversity in subunit composition: the receptor core is assembled from GABAB1a/b, GABAB2, four KCTD proteins and a distinct set of G-protein subunits, whereas the receptor's periphery is mostly formed by transmembrane proteins of different classes. In particular, the periphery-forming constituents include signaling effectors, such as Cav2 and HCN channels, and the proteins AJAP1 and amyloid-β A4, both of which tightly associate with the sushi domains of GABAB1a. Our results unravel the molecular diversity of GABAB receptors and their postnatal assembly dynamics and provide a roadmap for studying the cellular signaling of this inhibitory neurotransmitter receptor.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1038/nn.4198
- PMID 26691831
- Persistent URL
- https://sonar.ch/global/documents/160069
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