ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
The short splice variant of the gamma 2 subunit acts as an external modulator of GABA(A) receptor function.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- GABACellular and molecular neurobiology · 2026Review
- Recruitment of Plasma Membrane GABA-A Receptors by Submembranous Gephyrin/Collybistin Clusters.Cellular and molecular neurobiology · 2022Article
- Activation of the Rat α1β2ε GABABiomolecules · 2022Article
- DM1 Transgenic Mice Exhibit Abnormal Neurotransmitter Homeostasis and Synaptic Plasticity in Association with RNA Foci and Mis-Splicing in the Hippocampus.International journal of molecular sciences · 2022Article
- Looking for Novelty in an "Old" Receptor: Recent Advances Toward Our Understanding of GABAFrontiers in neuroscience · 2020Review
- γ2 GABAFrontiers in cellular neuroscience · 2018Review
- Comparison of γ-Aminobutyric Acid, Type A (GABAA), Receptor αβγ and αβδ Expression Using Flow Cytometry and Electrophysiology: EVIDENCE FOR ALTERNATIVE SUBUNIT STOICHIOMETRIES AND ARRANGEMENTS.The Journal of biological chemistry · 2016Article
- PX-RICS-deficient mice mimic autism spectrum disorder in Jacobsen syndrome through impaired GABAA receptor trafficking.Nature communications · 2016Article
- Three epilepsy-associated GABRG2 missense mutations at the γ+/β- interface disrupt GABAA receptor assembly and trafficking by similar mechanisms but to different extents.Neurobiology of disease · 2014Article
- Article
- Benzodiazepines modulate GABAA receptors by regulating the preactivation step after GABA binding.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Characteristics of concatemeric GABA(A) receptors containing α4/δ subunits expressed in Xenopus oocytes.British journal of pharmacology · 2012Article
- Article
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Authors and funding
3 authors.
Funding
Abstract
GABA(A) receptors (GABA(A)Rs) regulate the majority of fast inhibition in the mammalian brain and are the target for multiple drug types, including sleep aids, anti-anxiety medication, anesthetics, alcohol, and neurosteroids. A variety of subunits, including the highly distributed gamma2, allow for pharmacologic and kinetic differences in particular brain regions. The two common splice variants gamma2S (short) and gamma2L (long) show different patterns of regional distribution both in adult brain and during the course of development, but show few notable differences when incorporated into pentameric receptors. However, results presented here show that the gamma2S variant can strongly affect both GABA(A)R pharmacology and kinetics by acting as an external modulator of fully formed receptors. Mutation of one serine residue can confer gamma2S-like properties to gamma2L subunits, and addition of a modified gamma2 N-terminal polypeptide to the cell surface recapitulates the pharmacological effect. Thus, rather than incorporation of a separate accessory protein as with voltage-gated channels, this is an example of an ion channel using a common subunit for dual purposes. The modified receptor properties conferred by accessory gamma2S have implications for understanding GABA(A)R pharmacology, receptor kinetics, stoichiometry, GABAergic signaling in the brain during development, and altered function in disease states such as epilepsy.
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Registered trials
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