ArticleThe Journal of biological chemistry2013
Up-regulation of GABA(B) receptor signaling by constitutive assembly with the K+ channel tetramerization domain-containing protein 12 (KCTD12).
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- GABAB-Dependent Negative Feedback Contributes to Earlier Epileptiform Discharge Termination Within Malformed Cortex.International journal of molecular sciences · 2026Article
- Male-specific lethal 1 (MSL1) promotes Erastin-induced ferroptosis in colon cancer cells by regulating the KCTD12-SLC7A11 axis.Cell death & disease · 2025Article
- Smooth operator(s): dialing up and down neurotransmitter responses by G-protein regulators.Trends in cell biology · 2025Review
- Intermittent fasting reprograms the brain proteome to prevent synaptic degeneration and cognitive impairment in vascular dementia.Theranostics · 2025Article
- Emerging modes of regulation of neuromodulatory G protein-coupled receptors.Trends in neurosciences · 2024Review
- Synaptotagmin-11 facilitates assembly of a presynaptic signaling complex in post-Golgi cargo vesicles.EMBO reports · 2024Article
- Article
- The role of GABAFrontiers in endocrinology · 2023Review
- KCTD8 and KCTD12 Facilitate Axonal Expression of GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Structural Basis of GABACurrent topics in behavioral neurosciences · 2022Review
- The emerging role of the KCTD proteins in cancer.Cell communication and signaling : CCS · 2021Review
- Lithium and GADL1 regulate glycogen synthase kinase-3 activity to modulate KCTD12 expression.Scientific reports · 2019Article
- KCTD: A new gene family involved in neurodevelopmental and neuropsychiatric disorders.CNS neuroscience & therapeutics · 2019Review
- Genome-wide association analysis reveals KCTD12 and miR-383-binding genes in the background of rumination.Translational psychiatry · 2019Article
- Article
- Diversity of structure and function of GABAProceedings of the Japan Academy. Series B, Physical and biological sciences · 2018Review
- KCTD12 promotes tumorigenesis by facilitating CDC25B/CDK1/Aurora A-dependent G2/M transition.Oncogene · 2017Article
- KCTD12 modulation of GABA(B) receptor function.Pharmacology research & perspectives · 2017Article
- KCTD Hetero-oligomers Confer Unique Kinetic Properties on Hippocampal GABAB Receptor-Induced K+ Currents.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Altered emotionality and neuronal excitability in mice lacking KCTD12, an auxiliary subunit of GABAB receptors associated with mood disorders.Translational psychiatry · 2015Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GABA(B) receptors are the G-protein coupled receptors (GPCRs) for GABA, the main inhibitory neurotransmitter in the central nervous system. Native GABA(B) receptors comprise principle and auxiliary subunits that regulate receptor properties in distinct ways. The principle subunits GABA(B1a), GABA(B1b), and GABA(B2) form fully functional heteromeric GABA(B(1a,2)) and GABA(B(1b,2)) receptors. Principal subunits regulate forward trafficking of the receptors from the endoplasmic reticulum to the plasma membrane and control receptor distribution to axons and dendrites. The auxiliary subunits KCTD8, -12, -12b, and -16 are cytosolic proteins that influence agonist potency and G-protein signaling of GABA(B(1a,2)) and GABA(B(1b,2)) receptors. Here, we used transfected cells to study assembly, surface trafficking, and internalization of GABA(B) receptors in the presence of the KCTD12 subunit. Using bimolecular fluorescence complementation and metabolic labeling, we show that GABA(B) receptors associate with KCTD12 while they reside in the endoplasmic reticulum. Glycosylation experiments support that association with KCTD12 does not influence maturation of the receptor complex. Immunoprecipitation and bioluminescence resonance energy transfer experiments demonstrate that KCTD12 remains associated with the receptor during receptor activity and receptor internalization from the cell surface. We further show that KCTD12 reduces constitutive receptor internalization and thereby increases the magnitude of receptor signaling at the cell surface. Accordingly, knock-out or knockdown of KCTD12 in cultured hippocampal neurons reduces the magnitude of the GABA(B) receptor-mediated K(+) current response. In summary, our experiments support that the up-regulation of functional GABA(B) receptors at the neuronal plasma membrane is an additional physiological role of the auxiliary subunit KCTD12.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.