ArticleThe Journal of biological chemistry2008
The sushi domains of secreted GABA(B1) isoforms selectively impair GABA(B) heteroreceptor function.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- SEZ6L2 Loss Disrupts Motor Coordination, Cognitive Function, and Synaptic Connectivity.bioRxiv : the preprint server for biology · 2026Article
- Monoallelic de novoScience advances · 2024Article
- Synapse Formation and Function Across Species: Ancient Roles for CCP, CUB, and TSP-1 Structural Domains.Frontiers in neuroscience · 2022Review
- Mechanisms and Regulation of Neuronal GABACurrent topics in behavioral neurosciences · 2022Review
- Spinal Inhibition of GABAB Receptors by the Extracellular Matrix Protein Fibulin-2 in Neuropathic Rats.Frontiers in cellular neuroscience · 2020Article
- Beyond the Ligand: Extracellular and Transcellular G Protein-Coupled Receptor Complexes in Physiology and Pharmacology.Pharmacological reviews · 2019Review
- Diversity of structure and function of GABAProceedings of the Japan Academy. Series B, Physical and biological sciences · 2018Review
- Towards a Better Understanding of GABAergic Remodeling in Alzheimer's Disease.International journal of molecular sciences · 2017Review
- Organization and functions of mGlu and GABANature · 2016Review
- Altered gamma-aminobutyric acid type B receptor subunit 1 splicing in alcoholics.Biological psychiatry · 2014Article
- Complex GABAB receptor complexes: how to generate multiple functionally distinct units from a single receptor.Frontiers in pharmacology · 2014Review
- GABAB receptor subtypes differentially modulate synaptic inhibition in the dentate gyrus to enhance granule cell output.British journal of pharmacology · 2013Article
- Sushi domains confer distinct trafficking profiles on GABAB receptors.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Regulation of neuronal GABA(B) receptor functions by subunit composition.Nature reviews. Neuroscience · 2012Review
- GABAB receptor complex as a potential target for tumor therapy.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2012Review
- G protein-coupled receptors in the hypothalamic paraventricular and supraoptic nuclei--serpentine gateways to neuroendocrine homeostasis.Frontiers in neuroendocrinology · 2012Review
- The oligomeric state sets GABA(B) receptor signalling efficacy.The EMBO journal · 2011Article
- Article
- Plasticity of postsynaptic, but not presynaptic, GABAB receptors in SSADH deficient mice.Experimental neurology · 2010Article
- GABAB receptor constituents revealed by tandem affinity purification from transgenic mice.The Journal of biological chemistry · 2010Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GABA(B) receptors are the G-protein-coupled receptors for gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain. GABA(B) receptors are promising drug targets for a wide spectrum of psychiatric and neurological disorders. Receptor subtypes exhibit no pharmacological differences and are based on the subunit isoforms GABA(B1a) and GABA(B1b). GABA(B1a) differs from GABA(B1b) in its ectodomain by the presence of a pair of conserved protein binding motifs, the sushi domains (SDs). Previous work showed that selectively GABA(B1a) contributes to heteroreceptors at glutamatergic terminals, whereas both GABA(B1a) and GABA(B1b) contribute to autoreceptors at GABAergic terminals or to postsynaptic receptors. Here, we describe GABA(B1j), a secreted GABA(B1) isoform comprising the two SDs. We show that the two SDs, when expressed as a soluble protein, bind to neuronal membranes with low nanomolar affinity. Soluble SD protein, when added at nanomolar concentrations to dissociated hippocampal neurons or to acute hippocampal slices, impairs the inhibitory effect of GABA(B) heteroreceptors on evoked and spontaneous glutamate release. In contrast, soluble SD protein neither impairs the activity of GABA(B) autoreceptors nor impairs the activity of postsynaptic GABA(B) receptors. We propose that soluble SD protein scavenges an extracellular binding partner that retains GABA(B1a)-containing heteroreceptors in proximity of the presynaptic release machinery. Soluble GABA(B1) isoforms like GABA(B1j) may therefore act as dominant-negative inhibitors of heteroreceptors and control the level of GABA(B)-mediated inhibition at glutamatergic terminals. Of importance for drug discovery, our data also demonstrate that it is possible to selectively impair GABA(B) heteroreceptors by targeting their SDs.
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