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

Schwenk, Jochen and Perez-Garci, Enrique and Schneider, Andy and Kollewe, Astrid and Gauthier-Kemper, Anne and Fritzius, Thorsten and Raveh, Adi and Dinamarca, Margarita C. and Hanuschkin, Alexander and Bildl, Wolfgang and Klingauf, Jürgen and Gassmann, Martin and Schulte, Uwe and Bettler, Bernhard and Fakler, Bernd. (2016) Modular composition and dynamics of native GABAB receptors identified by high-resolution proteomics. Natural Neuroscience, 19 (2). pp. 233-242.

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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-beta 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Physiology > Molecular Neurobiology Synaptic Plasticity (Bettler)
UniBasel Contributors:Bettler, Bernhard
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1546-1726 (Electronic) 1097-6256 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:19 Jan 2019 18:40
Deposited On:19 Jan 2019 18:40

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