{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:52:00Z","timestamp":1791525120781,"version":"4.3.4"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>\n                    Glycine receptors (GlyRs) are chloride permeable ligand-gated ion channels that play an important role in synaptic transmission in the central nervous system. Besides glycine as neurotransmitter, cesium (Cs\n                    <jats:sup>+<\/jats:sup>\n                    ) was shown to activate homomeric GlyRs with \u03b12 and \u03b13 subunits, and a recent study revealed the position D194 as essential for activation of RNA-edited GlyR \u03b13\n                    <jats:sup>185L<\/jats:sup>\n                    at the cell surface. This position in the N-terminal extracellular ligand-binding domain belongs to a series of amino acid positions (D141, E192, D194 and D91, D97, E110, D114, Y161) predicted to be involved in Cs\n                    <jats:sup>+<\/jats:sup>\n                    binding. In the present study, we mutated the negatively charged amino acids D91, D97, E110, and D114 as well as the neutral polar amino acid Y161 to code for alanine with a neutral hydrophobic side chain or lysine with a positively charged side chain and performed patch-clamp analysis as well as surface GlyR staining using transfected HEK293T cells. We found that substitutions D97A\/K and Y161K resulted in a complete loss of receptor function in response to glycine or Cs\n                    <jats:sup>+<\/jats:sup>\n                    , whereas mutations at D91 and E110 retained detectable current responses, with E110A\/K mainly affecting glycine-evoked currents. Y161A retained at least some Cs\n                    <jats:sup>+<\/jats:sup>\n                    -dependent GlyR responsiveness at concentrations above 5 mM, indicating that a positive charge (K) at position Y161 is detrimental to glycine-dependent GlyR activation. However, as no mutant was identified that responded to glycine while lacking Cs\n                    <jats:sup>+<\/jats:sup>\n                    -evoked activity, these findings suggest that Cs\n                    <jats:sup>+<\/jats:sup>\n                    -mediated GlyR activation involves the same structural framework required for glycine-induced channel opening.\n                  <\/jats:p>","DOI":"10.3389\/fnmol.2026.1918246","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:33:32Z","timestamp":1791524012000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of critical sites for glycine- and cesium-dependent activation of the RNA-edited glycine receptor \u03b13L"],"prefix":"10.3389","volume":"19","author":[{"given":"Yulia","family":"Novykova","sequence":"first","affiliation":[{"name":"Division Cell Physiology, Institute for Cell- and Neurobiology, Technical University Braunschweig","place":["Braunschweig, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Fricke","sequence":"additional","affiliation":[{"name":"Division Cell Physiology, Institute for Cell- and Neurobiology, Technical University Braunschweig","place":["Braunschweig, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen C.","family":"Meier","sequence":"additional","affiliation":[{"name":"Division Cell Physiology, Institute for Cell- and Neurobiology, Technical University Braunschweig","place":["Braunschweig, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2325","DOI":"10.1093\/cercor\/bhw001","article-title":"Identification of parvalbumin interneurons as cellular substrate of fear memory persistence","volume":"26","author":"\u00c7aliskan","year":"2016","journal-title":"Cereb. 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