Structure and Mechanism of Kainate Receptor Modulation by Anions
L-glutamate, the major excitatory neurotransmitter in the human brain, activates a family of ligand-gated ion channels, the major subtypes of which are named AMPA, kainate, and NMDA receptors. In common with many signal transduction proteins, glutamate receptors are modulated by ions and small molec...
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| Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 2007-03, Vol.53 (6), p.829-841 |
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| creator | Plested, Andrew J.R. Mayer, Mark L. |
| description | L-glutamate, the major excitatory neurotransmitter in the human brain, activates a family of ligand-gated ion channels, the major subtypes of which are named AMPA, kainate, and NMDA receptors. In common with many signal transduction proteins, glutamate receptors are modulated by ions and small molecules, including Ca
2+, Mg
2+, Zn
2+, protons, polyamines, and steroids. Strikingly, the activation of kainate receptors by glutamate requires the presence of both Na
+ and Cl
− in the extracellular solution, and in the absence of these ions, receptor activity is abolished. Here, we identify the site and mechanism of action of anions. Surprisingly, we find that Cl
− ions are essential structural components of kainate receptors. Cl
− ions bind in a cavity formed at the interface between subunits in a dimer pair. In the absence of Cl
−, dimer stability is reduced, the rate of desensitization increases, and the fraction of receptors competent for activation by glutamate drops precipitously. |
| doi_str_mv | 10.1016/j.neuron.2007.02.025 |
| format | Article |
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2+, Mg
2+, Zn
2+, protons, polyamines, and steroids. Strikingly, the activation of kainate receptors by glutamate requires the presence of both Na
+ and Cl
− in the extracellular solution, and in the absence of these ions, receptor activity is abolished. Here, we identify the site and mechanism of action of anions. Surprisingly, we find that Cl
− ions are essential structural components of kainate receptors. Cl
− ions bind in a cavity formed at the interface between subunits in a dimer pair. In the absence of Cl
−, dimer stability is reduced, the rate of desensitization increases, and the fraction of receptors competent for activation by glutamate drops precipitously.</description><identifier>ISSN: 0896-6273</identifier><identifier>EISSN: 1097-4199</identifier><identifier>DOI: 10.1016/j.neuron.2007.02.025</identifier><identifier>PMID: 17359918</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Anions - pharmacology ; Binding sites ; Binding Sites - drug effects ; Cell Line, Transformed ; Crystallography - methods ; Drug Interactions ; Glutamic Acid - pharmacology ; Humans ; Ligands ; Membrane Potentials - drug effects ; Membrane Potentials - radiation effects ; Models, Molecular ; MOLNEURO ; Mutagenesis - physiology ; Neural networks ; Patch-Clamp Techniques ; Polyamines ; Protein Conformation - drug effects ; PROTEINS ; Receptors, Kainic Acid - chemistry ; Receptors, Kainic Acid - drug effects ; SIGNALING ; Structure-Activity Relationship ; Transfection - methods</subject><ispartof>Neuron (Cambridge, Mass.), 2007-03, Vol.53 (6), p.829-841</ispartof><rights>2007 Elsevier Inc.</rights><rights>Copyright Elsevier Limited Mar 15, 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c531t-7808921260d0623669ceb6cddeea7588282dea27eacc9957b44572516769ff3a3</citedby><cites>FETCH-LOGICAL-c531t-7808921260d0623669ceb6cddeea7588282dea27eacc9957b44572516769ff3a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.neuron.2007.02.025$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17359918$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Plested, Andrew J.R.</creatorcontrib><creatorcontrib>Mayer, Mark L.</creatorcontrib><title>Structure and Mechanism of Kainate Receptor Modulation by Anions</title><title>Neuron (Cambridge, Mass.)</title><addtitle>Neuron</addtitle><description>L-glutamate, the major excitatory neurotransmitter in the human brain, activates a family of ligand-gated ion channels, the major subtypes of which are named AMPA, kainate, and NMDA receptors. In common with many signal transduction proteins, glutamate receptors are modulated by ions and small molecules, including Ca
2+, Mg
2+, Zn
2+, protons, polyamines, and steroids. Strikingly, the activation of kainate receptors by glutamate requires the presence of both Na
+ and Cl
− in the extracellular solution, and in the absence of these ions, receptor activity is abolished. Here, we identify the site and mechanism of action of anions. Surprisingly, we find that Cl
− ions are essential structural components of kainate receptors. Cl
− ions bind in a cavity formed at the interface between subunits in a dimer pair. In the absence of Cl
−, dimer stability is reduced, the rate of desensitization increases, and the fraction of receptors competent for activation by glutamate drops precipitously.</description><subject>Anions - pharmacology</subject><subject>Binding sites</subject><subject>Binding Sites - drug effects</subject><subject>Cell Line, Transformed</subject><subject>Crystallography - methods</subject><subject>Drug Interactions</subject><subject>Glutamic Acid - pharmacology</subject><subject>Humans</subject><subject>Ligands</subject><subject>Membrane Potentials - drug effects</subject><subject>Membrane Potentials - radiation effects</subject><subject>Models, Molecular</subject><subject>MOLNEURO</subject><subject>Mutagenesis - physiology</subject><subject>Neural networks</subject><subject>Patch-Clamp Techniques</subject><subject>Polyamines</subject><subject>Protein Conformation - drug effects</subject><subject>PROTEINS</subject><subject>Receptors, Kainic Acid - chemistry</subject><subject>Receptors, Kainic Acid - drug effects</subject><subject>SIGNALING</subject><subject>Structure-Activity Relationship</subject><subject>Transfection - methods</subject><issn>0896-6273</issn><issn>1097-4199</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LAzEQhoMoWqv_QGRB8LZrkt0km4tYil-oCH6cQ5rMYkqb1GRX8N-b0oLgQRiYOTwz8_IgdEJwRTDhF_PKwxCDryjGosI0F9tBI4KlKBsi5S4a4VbyklNRH6DDlOYYk4ZJso8OiKiZlKQdoavXPg6mHyIU2tviCcyH9i4ti9AVD9p53UPxAgZWfYjFU7DDQvcu-GL2XUx8HtIR2uv0IsHxto_R-8312_SufHy-vZ9OHkvDatKXos1hKKEcW8xpzbk0MOPGWgAtWNvSllrQVIA2RkomZk3DBGWECy67rtb1GJ1v7q5i-Bwg9WrpkoHFQnsIQ1IUi5bJWmTw7A84D0P0OZsiDOfPjZBrqtlQJoaUInRqFd1Sx29FsFr7VXO18avWfhWmuVheO90eH2ZLsL9LW6EZuNwAkF18OYgqGQfegHURTK9scP9_-AEP04w_</recordid><startdate>20070315</startdate><enddate>20070315</enddate><creator>Plested, Andrew J.R.</creator><creator>Mayer, Mark L.</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20070315</creationdate><title>Structure and Mechanism of Kainate Receptor Modulation by Anions</title><author>Plested, Andrew J.R. ; 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In common with many signal transduction proteins, glutamate receptors are modulated by ions and small molecules, including Ca
2+, Mg
2+, Zn
2+, protons, polyamines, and steroids. Strikingly, the activation of kainate receptors by glutamate requires the presence of both Na
+ and Cl
− in the extracellular solution, and in the absence of these ions, receptor activity is abolished. Here, we identify the site and mechanism of action of anions. Surprisingly, we find that Cl
− ions are essential structural components of kainate receptors. Cl
− ions bind in a cavity formed at the interface between subunits in a dimer pair. In the absence of Cl
−, dimer stability is reduced, the rate of desensitization increases, and the fraction of receptors competent for activation by glutamate drops precipitously.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>17359918</pmid><doi>10.1016/j.neuron.2007.02.025</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; ScienceDirect; Cell Press Archives; EZB-FREE-00999 freely available EZB journals |
| subjects | Anions - pharmacology Binding sites Binding Sites - drug effects Cell Line, Transformed Crystallography - methods Drug Interactions Glutamic Acid - pharmacology Humans Ligands Membrane Potentials - drug effects Membrane Potentials - radiation effects Models, Molecular MOLNEURO Mutagenesis - physiology Neural networks Patch-Clamp Techniques Polyamines Protein Conformation - drug effects PROTEINS Receptors, Kainic Acid - chemistry Receptors, Kainic Acid - drug effects SIGNALING Structure-Activity Relationship Transfection - methods |
| title | Structure and Mechanism of Kainate Receptor Modulation by Anions |
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