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Nat Neurosci. 2016 Feb;19(2):233-42. doi: 10.1038/nn.4198. Epub 2015 Dec 21.

Modular composition and dynamics of native GABAB receptors identified by high-resolution proteomics.

Author information

1
Institute of Physiology, University of Freiburg, Freiburg, Germany.
2
Center for Biological Signaling Studies (BIOSS), Freiburg, Germany.
3
Department of Biomedicine, Institute of Physiology, Pharmazentrum, University of Basel, Basel, Switzerland.
4
Department of Cellular Biophysics, Institute of Medical Physics and Biophysics, University of Münster, Münster, Germany.
5
Optophysiology Lab, Department of Biology, University of Freiburg, Freiburg, Germany.
6
Logopharm GmbH, Freiburg, Germany.

Abstract

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.

PMID:
26691831
DOI:
10.1038/nn.4198
[Indexed for MEDLINE]

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