Modular composition and dynamics of native GABAB receptors identified by high-resolution proteomics
Schwenk at al., Nature Neuroscience online, http://dx.doi.org/10.1038/nn.4198
Dec 22, 2015
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. Here we use high-resolution functional proteomics to identify the building blocks of these receptors in the rodent brain. The analyses demonstrated 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, while the receptors’ 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-bA4 both of which tightly associate with the sushi-domains of GABAB1a. The 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.