Allosteric Interactions between NMDA Receptor Subunits Shape the Developmental Shift in Channel Properties
During development of the central nervous system, there is a shift in the subunit composition of NMDA receptors (NMDARs) resulting in a dramatic acceleration of NMDAR-mediated synaptic currents. This shift coincides with upregulation of the GluN2A subunit and triheteromeric GluN1/2A/2B receptors wit...
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| Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 2017-04, Vol.94 (1), p.58-64.e3 |
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| description | During development of the central nervous system, there is a shift in the subunit composition of NMDA receptors (NMDARs) resulting in a dramatic acceleration of NMDAR-mediated synaptic currents. This shift coincides with upregulation of the GluN2A subunit and triheteromeric GluN1/2A/2B receptors with fast deactivation kinetics, whereas expression of diheteromeric GluN1/2B receptors with slower deactivation kinetics is decreased. Here, we show that allosteric interactions occur between the glutamate-binding GluN2 subunits in triheteromeric GluN1/2A/2B NMDARs. This allosterism is dominated by the GluN2A subunit and results in functional properties not predicted by those of diheteromeric GluN1/2A and GluN1/2B NMDARs. These findings suggest that GluN1/2A/2B NMDARs may maintain some signaling properties of the GluN2B subunit while having the kinetic properties of GluN1/2A NMDARs and highlight the complexity in NMDAR signaling created by diversity in subunit composition.
•Allosterism occurs between GluN2 subunits in triheteromeric GluN1/2A/2B NMDARs•These allosteric interactions are asymmetric and dominated by the GluN2A subunit•GluN2A-dominant interactions span multiple domains in the NMDAR•The allosteric interactions endow GluN1/2A/2B with the function of GluN1/2A NMDARs
Sun et al. demonstrate asymmetric inter-GluN2 allosteric interactions within triheteromeric GluN1/2A/2B NMDARs that result in open probability and deactivation kinetics similar to diheteromeric GluN1/2A receptors. This finding highlights the complexity in NMDAR signaling endowed by diversity in subunit composition. |
| doi_str_mv | 10.1016/j.neuron.2017.03.018 |
| format | Article |
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•Allosterism occurs between GluN2 subunits in triheteromeric GluN1/2A/2B NMDARs•These allosteric interactions are asymmetric and dominated by the GluN2A subunit•GluN2A-dominant interactions span multiple domains in the NMDAR•The allosteric interactions endow GluN1/2A/2B with the function of GluN1/2A NMDARs
Sun et al. demonstrate asymmetric inter-GluN2 allosteric interactions within triheteromeric GluN1/2A/2B NMDARs that result in open probability and deactivation kinetics similar to diheteromeric GluN1/2A receptors. This finding highlights the complexity in NMDAR signaling endowed by diversity in subunit composition.</description><identifier>ISSN: 0896-6273</identifier><identifier>EISSN: 1097-4199</identifier><identifier>DOI: 10.1016/j.neuron.2017.03.018</identifier><identifier>PMID: 28384476</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Abundance ; Activation ; Activation analysis ; allosteric interaction ; Allosteric properties ; Allosteric Regulation - genetics ; amino-terminal domain ; Animals ; Binding sites ; Ca2+/calmodulin-dependent protein kinase II ; Casein kinase II ; Central nervous system ; Channel gating ; Chemical bonds ; Circuits ; Couples ; crosslinking ; Deactivation ; Endoplasmic Reticulum ; excitatory synaptic transmission ; Forebrain ; Gene Expression Regulation, Developmental ; GluN2 subunit ; glutamate ; Glutamic Acid - metabolism ; Glutamic acid receptors (ionotropic) ; HEK293 Cells ; Hippocampus ; Humans ; Ion channels ; Long-term potentiation ; Neuronal Plasticity ; Neurons ; Neurotransmission ; Ocular dominance ; Oocytes - metabolism ; open probability ; Patch-Clamp Techniques ; Protein Subunits ; Rats ; receptor deactivation ; Receptor mechanisms ; Receptors, N-Methyl-D-Aspartate - genetics ; Receptors, N-Methyl-D-Aspartate - metabolism ; Retention ; Revisions ; Rodents ; Synaptic Transmission ; Triheteromeric NMDA receptors ; Xenopus laevis</subject><ispartof>Neuron (Cambridge, Mass.), 2017-04, Vol.94 (1), p.58-64.e3</ispartof><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Apr 5, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-950f5389f1066a7ba845e8674cc5e25fd4c65140a709f05d2007416e675e391b3</citedby><cites>FETCH-LOGICAL-c491t-950f5389f1066a7ba845e8674cc5e25fd4c65140a709f05d2007416e675e391b3</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.2017.03.018$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28384476$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sun, Weinan</creatorcontrib><creatorcontrib>Hansen, Kasper B.</creatorcontrib><creatorcontrib>Jahr, Craig E.</creatorcontrib><title>Allosteric Interactions between NMDA Receptor Subunits Shape the Developmental Shift in Channel Properties</title><title>Neuron (Cambridge, Mass.)</title><addtitle>Neuron</addtitle><description>During development of the central nervous system, there is a shift in the subunit composition of NMDA receptors (NMDARs) resulting in a dramatic acceleration of NMDAR-mediated synaptic currents. This shift coincides with upregulation of the GluN2A subunit and triheteromeric GluN1/2A/2B receptors with fast deactivation kinetics, whereas expression of diheteromeric GluN1/2B receptors with slower deactivation kinetics is decreased. Here, we show that allosteric interactions occur between the glutamate-binding GluN2 subunits in triheteromeric GluN1/2A/2B NMDARs. This allosterism is dominated by the GluN2A subunit and results in functional properties not predicted by those of diheteromeric GluN1/2A and GluN1/2B NMDARs. These findings suggest that GluN1/2A/2B NMDARs may maintain some signaling properties of the GluN2B subunit while having the kinetic properties of GluN1/2A NMDARs and highlight the complexity in NMDAR signaling created by diversity in subunit composition.
•Allosterism occurs between GluN2 subunits in triheteromeric GluN1/2A/2B NMDARs•These allosteric interactions are asymmetric and dominated by the GluN2A subunit•GluN2A-dominant interactions span multiple domains in the NMDAR•The allosteric interactions endow GluN1/2A/2B with the function of GluN1/2A NMDARs
Sun et al. demonstrate asymmetric inter-GluN2 allosteric interactions within triheteromeric GluN1/2A/2B NMDARs that result in open probability and deactivation kinetics similar to diheteromeric GluN1/2A receptors. This finding highlights the complexity in NMDAR signaling endowed by diversity in subunit composition.</description><subject>Abundance</subject><subject>Activation</subject><subject>Activation analysis</subject><subject>allosteric interaction</subject><subject>Allosteric properties</subject><subject>Allosteric Regulation - genetics</subject><subject>amino-terminal domain</subject><subject>Animals</subject><subject>Binding sites</subject><subject>Ca2+/calmodulin-dependent protein kinase II</subject><subject>Casein kinase II</subject><subject>Central nervous system</subject><subject>Channel gating</subject><subject>Chemical bonds</subject><subject>Circuits</subject><subject>Couples</subject><subject>crosslinking</subject><subject>Deactivation</subject><subject>Endoplasmic Reticulum</subject><subject>excitatory synaptic transmission</subject><subject>Forebrain</subject><subject>Gene Expression Regulation, Developmental</subject><subject>GluN2 subunit</subject><subject>glutamate</subject><subject>Glutamic Acid - metabolism</subject><subject>Glutamic acid receptors (ionotropic)</subject><subject>HEK293 Cells</subject><subject>Hippocampus</subject><subject>Humans</subject><subject>Ion channels</subject><subject>Long-term potentiation</subject><subject>Neuronal Plasticity</subject><subject>Neurons</subject><subject>Neurotransmission</subject><subject>Ocular dominance</subject><subject>Oocytes - metabolism</subject><subject>open probability</subject><subject>Patch-Clamp Techniques</subject><subject>Protein Subunits</subject><subject>Rats</subject><subject>receptor deactivation</subject><subject>Receptor mechanisms</subject><subject>Receptors, N-Methyl-D-Aspartate - genetics</subject><subject>Receptors, N-Methyl-D-Aspartate - metabolism</subject><subject>Retention</subject><subject>Revisions</subject><subject>Rodents</subject><subject>Synaptic Transmission</subject><subject>Triheteromeric NMDA receptors</subject><subject>Xenopus laevis</subject><issn>0896-6273</issn><issn>1097-4199</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1v1DAQjRCILoV_gJAlLlwS7MSfF6TVlkKl8iEKZ8txJqxXWTvYzqL-e1y2lI8Dp5Fm3nszb15VPSW4IZjwl7vGwxKDb1pMRIO7BhN5r1oRrERNiVL3qxWWite8Fd1J9SilHcaEMkUeViet7CSlgq-q3XqaQsoQnUUXvlRjsws-oR7ydwCP3r87W6NPYGHOIaKrpV-8ywldbc0MKG8BncEBpjDvwWczlb4bM3IebbbGe5jQxxhmiNlBelw9GM2U4MltPa2-nL_-vHlbX354c7FZX9aWKpJrxfDIOqlGgjk3ojeSMpBcUGsZtGwcqOWMUGwEViNmQ4uxoIQDFww6RfrutHp11J2Xfg-DLYdFM-k5ur2J1zoYp_-eeLfVX8NBs0JXShaBF7cCMXxbIGW9d8nCNBkPYUmaSMkU5UJ2Bfr8H-guLNEXez9RWNHy84KiR5SNIaUI490xBOubMPVOH8PUN2Fq3OkSZqE9-9PIHelXer-dQnnnwUHUyTrwFgYXwWY9BPf_DT8ATvezPQ</recordid><startdate>20170405</startdate><enddate>20170405</enddate><creator>Sun, Weinan</creator><creator>Hansen, Kasper B.</creator><creator>Jahr, Craig E.</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><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170405</creationdate><title>Allosteric Interactions between NMDA Receptor Subunits Shape the Developmental Shift in Channel Properties</title><author>Sun, Weinan ; Hansen, Kasper B. ; Jahr, Craig E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-950f5389f1066a7ba845e8674cc5e25fd4c65140a709f05d2007416e675e391b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Abundance</topic><topic>Activation</topic><topic>Activation analysis</topic><topic>allosteric interaction</topic><topic>Allosteric properties</topic><topic>Allosteric Regulation - genetics</topic><topic>amino-terminal domain</topic><topic>Animals</topic><topic>Binding sites</topic><topic>Ca2+/calmodulin-dependent protein kinase II</topic><topic>Casein kinase II</topic><topic>Central nervous system</topic><topic>Channel gating</topic><topic>Chemical bonds</topic><topic>Circuits</topic><topic>Couples</topic><topic>crosslinking</topic><topic>Deactivation</topic><topic>Endoplasmic Reticulum</topic><topic>excitatory synaptic transmission</topic><topic>Forebrain</topic><topic>Gene Expression Regulation, Developmental</topic><topic>GluN2 subunit</topic><topic>glutamate</topic><topic>Glutamic Acid - metabolism</topic><topic>Glutamic acid receptors (ionotropic)</topic><topic>HEK293 Cells</topic><topic>Hippocampus</topic><topic>Humans</topic><topic>Ion channels</topic><topic>Long-term potentiation</topic><topic>Neuronal Plasticity</topic><topic>Neurons</topic><topic>Neurotransmission</topic><topic>Ocular dominance</topic><topic>Oocytes - metabolism</topic><topic>open probability</topic><topic>Patch-Clamp Techniques</topic><topic>Protein Subunits</topic><topic>Rats</topic><topic>receptor deactivation</topic><topic>Receptor mechanisms</topic><topic>Receptors, N-Methyl-D-Aspartate - genetics</topic><topic>Receptors, N-Methyl-D-Aspartate - metabolism</topic><topic>Retention</topic><topic>Revisions</topic><topic>Rodents</topic><topic>Synaptic Transmission</topic><topic>Triheteromeric NMDA receptors</topic><topic>Xenopus laevis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Weinan</creatorcontrib><creatorcontrib>Hansen, Kasper B.</creatorcontrib><creatorcontrib>Jahr, Craig E.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neuron (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Weinan</au><au>Hansen, Kasper B.</au><au>Jahr, Craig E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Allosteric Interactions between NMDA Receptor Subunits Shape the Developmental Shift in Channel Properties</atitle><jtitle>Neuron (Cambridge, Mass.)</jtitle><addtitle>Neuron</addtitle><date>2017-04-05</date><risdate>2017</risdate><volume>94</volume><issue>1</issue><spage>58</spage><epage>64.e3</epage><pages>58-64.e3</pages><issn>0896-6273</issn><eissn>1097-4199</eissn><abstract>During development of the central nervous system, there is a shift in the subunit composition of NMDA receptors (NMDARs) resulting in a dramatic acceleration of NMDAR-mediated synaptic currents. This shift coincides with upregulation of the GluN2A subunit and triheteromeric GluN1/2A/2B receptors with fast deactivation kinetics, whereas expression of diheteromeric GluN1/2B receptors with slower deactivation kinetics is decreased. Here, we show that allosteric interactions occur between the glutamate-binding GluN2 subunits in triheteromeric GluN1/2A/2B NMDARs. This allosterism is dominated by the GluN2A subunit and results in functional properties not predicted by those of diheteromeric GluN1/2A and GluN1/2B NMDARs. These findings suggest that GluN1/2A/2B NMDARs may maintain some signaling properties of the GluN2B subunit while having the kinetic properties of GluN1/2A NMDARs and highlight the complexity in NMDAR signaling created by diversity in subunit composition.
•Allosterism occurs between GluN2 subunits in triheteromeric GluN1/2A/2B NMDARs•These allosteric interactions are asymmetric and dominated by the GluN2A subunit•GluN2A-dominant interactions span multiple domains in the NMDAR•The allosteric interactions endow GluN1/2A/2B with the function of GluN1/2A NMDARs
Sun et al. demonstrate asymmetric inter-GluN2 allosteric interactions within triheteromeric GluN1/2A/2B NMDARs that result in open probability and deactivation kinetics similar to diheteromeric GluN1/2A receptors. This finding highlights the complexity in NMDAR signaling endowed by diversity in subunit composition.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28384476</pmid><doi>10.1016/j.neuron.2017.03.018</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Abundance Activation Activation analysis allosteric interaction Allosteric properties Allosteric Regulation - genetics amino-terminal domain Animals Binding sites Ca2+/calmodulin-dependent protein kinase II Casein kinase II Central nervous system Channel gating Chemical bonds Circuits Couples crosslinking Deactivation Endoplasmic Reticulum excitatory synaptic transmission Forebrain Gene Expression Regulation, Developmental GluN2 subunit glutamate Glutamic Acid - metabolism Glutamic acid receptors (ionotropic) HEK293 Cells Hippocampus Humans Ion channels Long-term potentiation Neuronal Plasticity Neurons Neurotransmission Ocular dominance Oocytes - metabolism open probability Patch-Clamp Techniques Protein Subunits Rats receptor deactivation Receptor mechanisms Receptors, N-Methyl-D-Aspartate - genetics Receptors, N-Methyl-D-Aspartate - metabolism Retention Revisions Rodents Synaptic Transmission Triheteromeric NMDA receptors Xenopus laevis |
| title | Allosteric Interactions between NMDA Receptor Subunits Shape the Developmental Shift in Channel Properties |
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