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• W2009094782 abstract "A tethered ligand approach reveals that four ligand molecules are required for full desensitization of tetrameric iGluR (glutamate receptor) channels. When fewer ligands are bound, which might be the case during synaptic transmission, desensitization is incomplete or non-existent. Cell signaling is often mediated by the binding of multiple ligands to multisubunit receptors. The probabilistic nature and sometimes slow rate of binding encountered with diffusible ligands can impede attempts to determine how the ligand occupancy controls signaling in such protein complexes. We describe a solution to this problem that uses a photoswitched tethered ligand as a 'ligand clamp' to induce rapid and stable binding and unbinding at defined subsets of subunits. We applied the approach to study gating in ionotropic glutamate receptors (iGluRs), ligand-gated ion channels that mediate excitatory neurotransmission and plasticity at glutamatergic synapses in the brain. We probed gating in two kainate-type iGluRs, GluK2 homotetramers and GluK2–GluK5 heterotetramers. Ultrafast (submillisecond) photoswitching of an azobenzene-based ligand on specific subunits provided a real-time measure of gating and revealed that partially occupied receptors can activate without desensitizing. The findings have implications for signaling by locally released and spillover glutamate." @default.
• W2009094782 created "2016-06-24" @default.
• W2009094782 creator A5074413118 @default.
• W2009094782 creator A5081378606 @default.
• W2009094782 date "2014-02-23" @default.
• W2009094782 modified "2023-09-29" @default.
• W2009094782 title "Tethered ligands reveal glutamate receptor desensitization depends on subunit occupancy" @default.
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• W2009094782 doi "https://doi.org/10.1038/nchembio.1458" @default.
• W2009094782 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4041372" @default.
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• W2009094782 hasPublicationYear "2014" @default.
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