ArticleThe EMBO journal2012
Impairment of GABAB receptor dimer by endogenous 14-3-3ζ in chronic pain conditions.
Article in The EMBO journal, 2012. 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 53 citations in OpenAlex.
- GABAMedComm · 2025Review
- Modulating GPCR and 14-3-3 protein interactions: Prospects for CNS drug discovery.Drug discovery today · 2023Review
- The role of GABAFrontiers in endocrinology · 2023Review
- Astrocytes mediate long-lasting synaptic regulation of ventral tegmental area dopamine neurons.Nature neuroscience · 2022Article
- Neuronal G protein-gated KAmerican journal of physiology. Cell physiology · 2022Review
- GABACurrent topics in behavioral neurosciences · 2022Review
- Mechanisms and Regulation of Neuronal GABACurrent topics in behavioral neurosciences · 2022Review
- MicroRNA-330 Directs Downregulation of the GABAJournal of molecular neuroscience : MN · 2020Article
- Spinal Inhibition of GABAB Receptors by the Extracellular Matrix Protein Fibulin-2 in Neuropathic Rats.Frontiers in cellular neuroscience · 2020Article
- Article
- Contribution of GABAergic modulation in DRGs to electroacupuncture analgesia in incisional neck pain rats.Journal of pain research · 2019Article
- The Retinitis Pigmentosa-Linked Mutations in Transmembrane Helix 5 of Rhodopsin Disrupt Cellular Trafficking Regardless of Oligomerization State.Biochemistry · 2018Article
- Calcium signalling through L-type calcium channels: role in pathophysiology of spinal nociceptive transmission.British journal of pharmacology · 2018Review
- Organization and functions of mGlu and GABANature · 2016Review
- GABAB receptor cell-surface export is controlled by an endoplasmic reticulum gatekeeper.Molecular psychiatry · 2016Article
- Rapid antidepressants stimulate the decoupling of GABA(B) receptors from GIRK/Kir3 channels through increased protein stability of 14-3-3η.Molecular psychiatry · 2015Article
- Baclofen, a GABABR agonist, ameliorates immune-complex mediated acute lung injury by modulating pro-inflammatory mediators.PloS one · 2015Article
- GABA pharmacology: the search for analgesics.Neurochemical research · 2014Review
- GINIP, a Gαi-interacting protein, functions as a key modulator of peripheral GABAB receptor-mediated analgesia.Neuron · 2014Article
- Complex GABAB receptor complexes: how to generate multiple functionally distinct units from a single receptor.Frontiers in pharmacology · 2014Review
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the central nervous system, the inhibitory GABAB receptor is the archetype of heterodimeric G protein-coupled receptors (GPCRs). However, the regulation of GABAB dimerization, and more generally of GPCR oligomerization, remains largely unknown. We propose a novel mechanism for inhibition of GPCR activity through de-dimerization in pathological conditions. We show here that 14-3-3ζ, a GABAB1-binding protein, dissociates the GABAB heterodimer, resulting in the impairment of GABAB signalling in spinal neurons. In the dorsal spinal cord of neuropathic rats, 14-3-3ζ is overexpressed and weakens GABAB inhibition. Using anti-14-3-3ζ siRNA or competing peptides disrupts 14-3-3ζ/GABAB1 interaction and restores functional GABAB heterodimers in the dorsal horn. Importantly, both strategies greatly enhance the anti-nociceptive effect of intrathecal Baclofen in neuropathic rats. Taken together, our data provide the first example of endogenous regulation of a GPCR oligomeric state and demonstrate its functional impact on the pathophysiological process of neuropathic pain sensitization.
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Registered trials
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.