Seminar
Abstract:
Cloned GABAB receptors do not reproduce kinetic and pharmacological properties (e.g. activation/deactivation kinetics, desensitization) of the native receptors [Pin & Bettler, Nature, 2016]. This observation raised the possibility that the functions of native GABAB receptors are influenced by receptor-associated proteins. Application of proteomic approaches to GABAB receptors yielded a comprehensive set of proteins that associate with native GABAB receptors [Schwenk et al., Nature Neuroscience, 2016]. We have started to analyze receptor-associated proteins for their effects on GABAB receptor physiology by using biochemical assays, electrophysiology, BRET, as well as manipulation of protein expression levels in mice. These studies allowed us to assign a receptor functions to a number of newly discovered proteome constituents. We also identified unanticipated GABAB receptor effectors such as the hyperpolarization-activated cyclic nucleotide-gated HCN channels and transient-receptor potential vanilloid-1 TRPV1 channels [Hanack et al., Cell, 2015; Schwenk et al., Nature Neuroscience, 2016]. The presentation will focus on the principles of GABAB receptor architecture and regulation emerging from the functional characterization of the receptor proteome.