Abstract
γ-AMINOBUTYRIC acid type-A (GABAA) receptors are the major sites of fast synaptic inhibition in the brain. They are presumed to be pentameric heteroligomers assembled from four classes of subunits with multiple members: α (1-6), β (1-3), γ (1-3) and δ (1)1-5. Here, GABAA receptors consisting of α1, β1 and γ2L sub-units, coexpressed in mammalian cells with the tyrosine kinase vSRC (the transforming gene product of the Rous sarcoma virus), were phosphorylated on tyrosine residues within the γ2L and β1 subunits. Tyrosine phosphorylation enhanced the whole-cell current induced by GABA. Site-specific mutagenesis of two tyrosine residues within the predicted intracellular domain of the γ2L sub-unit abolished tyrosine phosphorylation of this subunit and eliminated receptor modulation. A similar modulation of GABAA receptor function was observed in primary neuronal cultures. As GABAA receptors are critical in mediating fast synaptic inhibition, such a regulation by tyrosine kinases may therefore have profound effects on the control of neuronal excitation.
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Moss, S., Gorrie, G., Amato, A. et al. Modulation of GABAA receptors by tyrosine phosphorylation . Nature 377, 344–348 (1995). https://doi.org/10.1038/377344a0
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DOI: https://doi.org/10.1038/377344a0
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