Modular composition and dynamics of native GABAB receptors identified by high-resolution proteomics
| Autor: | Astrid Kollewe, Andy Schneider, Jochen Schwenk, Enrique Pérez-Garci, Anne Gauthier-Kemper, Adi Raveh, Jürgen Klingauf, Bernd Fakler, Bernhard Bettler, Alexander Hanuschkin, Wolfgang Bildl, Uwe Schulte, Margarita C. Dinamarca, Thorsten Fritzius, Martin Gassmann |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Proteomics Cell signaling Caveolin 2 Molecular neuroscience GABAB receptor Biology Rhodopsin-like receptors Receptors G-Protein-Coupled 03 medical and health sciences Amyloid beta-Protein Precursor Epitopes Mice Animals Rats Wistar Receptor Mice Knockout Mice Inbred BALB C General Neuroscience Cell Membrane Rats 030104 developmental biology Metabotropic receptor Receptors GABA-B Signal transduction Neuroscience Signal Transduction |
| Zdroj: | Nature neuroscience nature neuroscience |
| ISSN: | 1546-1726 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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