Journal
NATURE NEUROSCIENCE
Volume 19, Issue 2, Pages 233-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.4198
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Funding
- Swiss Science Foundation [31003A-152970]
- National Center for Competences in Research (NCCR) 'Synapsy, Synaptic Basis of Mental Health Disease'
- Deutsche Forschungsgemeinschaft [SFB 746/TP16, Fa 332/9-1, Fa 332/9-2]
- Swiss National Science Foundation (SNF) [31003A_152970] Funding Source: Swiss National Science Foundation (SNF)
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GABA(B) 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 GABA(B) receptors are macromolecular complexes with defined architecture, but marked diversity in subunit composition: the receptor core is assembled from GABA(B1a/b), GABA(B2), 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 GABA(B1a). 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.
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