ArticleThe Journal of biological chemistry2012
Opposite effects of KCTD subunit domains on GABA(B) receptor-mediated desensitization.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- GABAFrontiers in pharmacology · 2026Review
- KCTD Family: Emerging Regulators of GPCR Biased Signaling.Handbook of experimental pharmacology · 2026Review
- Genomic analyses in Cavalier King Charles spaniels identify loci associated with clinical signs of Chiari-like malformation and Syringomyelia.BMC veterinary research · 2025Article
- Smooth operator(s): dialing up and down neurotransmitter responses by G-protein regulators.Trends in cell biology · 2025Review
- Synaptotagmin-11 facilitates assembly of a presynaptic signaling complex in post-Golgi cargo vesicles.EMBO reports · 2024Article
- Structural basis for the ubiquitination of G protein βγ subunits by KCTD5/Cullin3 E3 ligase.Science advances · 2023Article
- IL-6-Mediated Upregulated miRNAs in Extracellular Vesicles Derived from Lund Human Mesencephalic (LUHMES) Cells: Effects on Astrocytes and Microglia.Biomolecules · 2023Article
- The role of GABAFrontiers in endocrinology · 2023Review
- Kctd7 deficiency induces myoclonic seizures associated with Purkinje cell death and microvascular defects.Disease models & mechanisms · 2022Article
- Keeping the Balance: GABABrain sciences · 2022Review
- 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
- GABACurrent topics in behavioral neurosciences · 2022Article
- Secreted Amyloid Precursor Protein Alpha, a Neuroprotective Protein in the Brain Has Widespread Effects on the Transcriptome and Proteome of Human Inducible Pluripotent Stem Cell-Derived Glutamatergic Neurons Related to Memory Mechanisms.Frontiers in neuroscience · 2022Article
- Why do platelets express KPlatelets · 2021Review
- GABAeLife · 2021Article
- Acute and Chronic Molecular Signatures and Associated Symptoms of Blast Exposure in Military Breachers.Journal of neurotrauma · 2020Article
- Target highlights in CASP13: Experimental target structures through the eyes of their authors.Proteins · 2019Article
- Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function.Neurochemistry international · 2019Article
- KCTD: A new gene family involved in neurodevelopmental and neuropsychiatric disorders.CNS neuroscience & therapeutics · 2019Review
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10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GABA(B) receptors assemble from principle and auxiliary subunits. The principle subunits GABA(B1) and GABA(B2) form functional heteromeric GABA(B(1,2)) receptors that associate with homotetramers of auxiliary KCTD8, -12, -12b, or -16 (named after their K(+) channel tetramerization domain) subunits. These auxiliary subunits constitute receptor subtypes with distinct functional properties. KCTD12 and -12b generate desensitizing receptor responses while KCTD8 and -16 generate largely non-desensitizing receptor responses. The structural elements of the KCTDs underlying these differences in desensitization are unknown. KCTDs are modular proteins comprising a T1 tetramerization domain, which binds to GABA(B2), and a H1 homology domain. KCTD8 and -16 contain an additional C-terminal H2 homology domain that is not sequence-related to the H1 domains. No functions are known for the H1 and H2 domains. Here we addressed which domains and sequence motifs in KCTD proteins regulate desensitization of the receptor response. We found that the H1 domains in KCTD12 and -12b mediate desensitization through a particular sequence motif, T/NFLEQ, which is not present in the H1 domains of KCTD8 and -16. In addition, the H2 domains in KCTD8 and -16 inhibit desensitization when expressed C-terminal to the H1 domains but not when expressed as a separate protein in trans. Intriguingly, the inhibitory effect of the H2 domain is sequence-independent, suggesting that the H2 domain sterically hinders desensitization by the H1 domain. Evolutionary analysis supports that KCTD12 and -12b evolved desensitizing properties by liberating their H1 domains from antagonistic H2 domains and acquisition of the T/NFLEQ motif.
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