GABAB receptors are the G-protein coupled receptors for the main inhibitory neurotransmitter in the brain, GABA. GABAB receptors were shown to associate with homo-oligomers of auxiliary KCTD8, KCTD12, KCTD12b, and KCTD16 subunits (named after their T1 K+-channel tetramerization domain) that regulate G-protein signaling of the receptor. Here we provide evidence that GABAB receptors also associate with hetero-oligomers of KCTD subunits. Coimmunoprecipitation experiments indicate that two-thirds of the KCTD16 proteins in the hippocampus of adult mice associate with KCTD12. We show that the KCTD proteins hetero-oligomerize through self-interacting T1 and H1 homology domains. Bioluminescence resonance energy transfer measurements in live cells reveal that KCTD12/KCTD16 hetero-oligomers associate with both the receptor and the G-protein. Electrophysiological experiments demonstrate that KCTD12/KCTD16 hetero-oligomers impart unique kinetic properties on G-protein-activated Kir3 currents. During prolonged receptor activation (one min) KCTD12/KCTD16 hetero-oligomers produce moderately desensitizing fast deactivating K+ currents, whereas KCTD12 and KCTD16 homo-oligomers produce strongly desensitizing fast deactivating currents and nondesensitizing slowly deactivating currents, respectively. During short activation (2 s) KCTD12/KCTD16 hetero-oligomers produce nondesensitizing slowly deactivating currents. Electrophysiological recordings from hippocampal neurons of KCTD knock-out mice are consistent with these findings and indicate that KCTD12/KCTD16 hetero-oligomers increase the duration of slow IPSCs. In summary, our data demonstrate that simultaneous assembly of distinct KCTDs at the receptor increases the molecular and functional repertoire of native GABAB receptors and modulates physiologically induced K+ current responses in the hippocampus.
Pubmed ID: 28003345 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This unknown targets IgG
View all literature mentionsThis monoclonal secondary targets IgG
View all literature mentionsThis unknown targets Guinea Pig IgG, whole molecule
View all literature mentionsThis monoclonal targets β-Tubulin III
View all literature mentionsThis monoclonal targets GABA(B)R2 (C44A4) Rabbit mAb
View all literature mentionsThis polyclonal targets FLAG
View all literature mentionsThis unknown targets c-Myc
View all literature mentionsThis polyclonal targets synthetic peptid, aa 7 - 23 of mouse KCTD16 protein (https://www.ncbi.nlm.nih.gov/protein/NP_808383.3)
View all literature mentionsThis monoclonal targets c-Myc
View all literature mentionsThis polyclonal targets synthetic peptid, aa 145 - 167 of mouse KCTD12 protein (https://www.ncbi.nlm.nih.gov/protein/NP_808383.3)
View all literature mentionsThis polyclonal targets synthetic peptid, aa 7 - 23 of mouse KCTD16 protein (https://www.ncbi.nlm.nih.gov/protein/NP_080411.1)
View all literature mentionsThis polyclonal targets synthetic peptid, aa 145 - 167 of mouse KCTD12 protein (https://www.ncbi.nlm.nih.gov/protein/NP_808383.3)
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsSoftware suite for electrophysiology data acquisition and analysis by Molecular Devices. Used for the control and recording of voltage clamp, current clamp, and patch clamp experiments. The software suite consists of Clampex 11 Software for data acquisition, AxoScope 11 Software for background recording, Clampfit 11 Software for data analysis, and optional Clampfit Advanced Analysis Module for sophisticated and streamlined analysis.
View all literature mentionsCell line CHO-K1 is a Spontaneously immortalized cell line with a species of origin Cricetulus griseus (Chinese hamster)
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsAllele Detail: Targeted This is a legacy resource.
View all literature mentions