Calmodulin Mediates Calcium-Dependent Inactivation of N-Methyl-D-Aspartate Receptors
Ca2+ influx through N-methyl-D-aspartate (NMDA) receptors activates signal transduction pathways critical for many forms of synaptic plasticity in the brain. NMDA receptor–mediated Ca2+ influx also downregulates the gating of NMDA channels through a process called Ca2+-dependent inactivation (CDI)....
Gespeichert in:
| Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 1998-08, Vol.21 (2), p.443-453 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 453 |
|---|---|
| container_issue | 2 |
| container_start_page | 443 |
| container_title | Neuron (Cambridge, Mass.) |
| container_volume | 21 |
| creator | Zhang, Su Ehlers, Michael D Bernhardt, Jeffery P Su, Ching-Tien Huganir, Richard L |
| description | Ca2+ influx through N-methyl-D-aspartate (NMDA) receptors activates signal transduction pathways critical for many forms of synaptic plasticity in the brain. NMDA receptor–mediated Ca2+ influx also downregulates the gating of NMDA channels through a process called Ca2+-dependent inactivation (CDI). Recent studies have demonstrated that the calcium binding protein calmodulin directly interacts with NMDA receptors, suggesting that calmodulin may play a role in CDI. We report here that the mutation of a specific calmodulin binding site in the C0 region of the NR1 subunit of the NMDA receptor blocks CDI. Moreover, intracellular infusion of a calmodulin inhibitory peptide markedly reduces CDI of both recombinant and neuronal NMDA receptors. Furthermore, this inactivating effect of calmodulin can be prevented by coexpressing a region of the cytoskeletal protein α-actinin2 known to interact with the C0 region of NR1. Taken together, these results demonstrate that the binding of Ca2+/calmodulin to NR1 mediates CDI of the NMDA receptor and suggest that inactivation occurs via Ca2+/calmodulin-dependent release of the receptor complex from the neuronal cytoskeleton. |
| doi_str_mv | 10.1016/S0896-6273(00)80553-X |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_17392112</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S089662730080553X</els_id><sourcerecordid>17392112</sourcerecordid><originalsourceid>FETCH-LOGICAL-c490t-732139615786fd37563559cc8f96695e7fcac741d194072c85dfba58e81079663</originalsourceid><addsrcrecordid>eNqFkEtLAzEUhYMotVZ_QmFWootoMjOZTFYirS9oFbRCdyFN7mBkXiaZQv-90wduXV2455x7uB9CY0puKKHZ7QfJRYazmCdXhFznhLEEL4_QkBLBcUqFOEbDP8spOvP-mxCaMkEHaCB4nIuYDdFiosqqMV1p62gOxqoAPup32nYVnkILtYE6RC-10sGuVbBNHTVF9IrnEL42JZ7ie98qF_pc9A4a2tA4f45OClV6uDjMEfp8fFhMnvHs7ellcj_DOhUkYJ7ENBEZZTzPCpNwliWMCa3zQmSZYMALrTRPqaEiJTzWOTPFSrEcckp4b0lG6HJ_t3XNTwc-yMp6DWWpamg6LylPRExp3BvZ3qhd472DQrbOVsptJCVyS1PuaMotKkmI3NGUyz43PhR0qwrMX-qAr9fv9jr0X64tOOm1hVr3IB3oIE1j_2n4BTkrg6k</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17392112</pqid></control><display><type>article</type><title>Calmodulin Mediates Calcium-Dependent Inactivation of N-Methyl-D-Aspartate Receptors</title><source>MEDLINE</source><source>Cell Press Free Archives</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Zhang, Su ; Ehlers, Michael D ; Bernhardt, Jeffery P ; Su, Ching-Tien ; Huganir, Richard L</creator><creatorcontrib>Zhang, Su ; Ehlers, Michael D ; Bernhardt, Jeffery P ; Su, Ching-Tien ; Huganir, Richard L</creatorcontrib><description>Ca2+ influx through N-methyl-D-aspartate (NMDA) receptors activates signal transduction pathways critical for many forms of synaptic plasticity in the brain. NMDA receptor–mediated Ca2+ influx also downregulates the gating of NMDA channels through a process called Ca2+-dependent inactivation (CDI). Recent studies have demonstrated that the calcium binding protein calmodulin directly interacts with NMDA receptors, suggesting that calmodulin may play a role in CDI. We report here that the mutation of a specific calmodulin binding site in the C0 region of the NR1 subunit of the NMDA receptor blocks CDI. Moreover, intracellular infusion of a calmodulin inhibitory peptide markedly reduces CDI of both recombinant and neuronal NMDA receptors. Furthermore, this inactivating effect of calmodulin can be prevented by coexpressing a region of the cytoskeletal protein α-actinin2 known to interact with the C0 region of NR1. Taken together, these results demonstrate that the binding of Ca2+/calmodulin to NR1 mediates CDI of the NMDA receptor and suggest that inactivation occurs via Ca2+/calmodulin-dependent release of the receptor complex from the neuronal cytoskeleton.</description><identifier>ISSN: 0896-6273</identifier><identifier>EISSN: 1097-4199</identifier><identifier>DOI: 10.1016/S0896-6273(00)80553-X</identifier><identifier>PMID: 9728925</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Actinin - analysis ; Animals ; Binding Sites ; Calcium - physiology ; Calmodulin - physiology ; Cell Line ; Down-Regulation ; Feedback ; Infusions, Parenteral ; Ion Channel Gating ; Mutagenesis, Site-Directed ; Neuronal Plasticity - physiology ; Point Mutation ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors ; Signal Transduction - physiology</subject><ispartof>Neuron (Cambridge, Mass.), 1998-08, Vol.21 (2), p.443-453</ispartof><rights>1998 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-732139615786fd37563559cc8f96695e7fcac741d194072c85dfba58e81079663</citedby><cites>FETCH-LOGICAL-c490t-732139615786fd37563559cc8f96695e7fcac741d194072c85dfba58e81079663</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0896-6273(00)80553-X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9728925$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Su</creatorcontrib><creatorcontrib>Ehlers, Michael D</creatorcontrib><creatorcontrib>Bernhardt, Jeffery P</creatorcontrib><creatorcontrib>Su, Ching-Tien</creatorcontrib><creatorcontrib>Huganir, Richard L</creatorcontrib><title>Calmodulin Mediates Calcium-Dependent Inactivation of N-Methyl-D-Aspartate Receptors</title><title>Neuron (Cambridge, Mass.)</title><addtitle>Neuron</addtitle><description>Ca2+ influx through N-methyl-D-aspartate (NMDA) receptors activates signal transduction pathways critical for many forms of synaptic plasticity in the brain. NMDA receptor–mediated Ca2+ influx also downregulates the gating of NMDA channels through a process called Ca2+-dependent inactivation (CDI). Recent studies have demonstrated that the calcium binding protein calmodulin directly interacts with NMDA receptors, suggesting that calmodulin may play a role in CDI. We report here that the mutation of a specific calmodulin binding site in the C0 region of the NR1 subunit of the NMDA receptor blocks CDI. Moreover, intracellular infusion of a calmodulin inhibitory peptide markedly reduces CDI of both recombinant and neuronal NMDA receptors. Furthermore, this inactivating effect of calmodulin can be prevented by coexpressing a region of the cytoskeletal protein α-actinin2 known to interact with the C0 region of NR1. Taken together, these results demonstrate that the binding of Ca2+/calmodulin to NR1 mediates CDI of the NMDA receptor and suggest that inactivation occurs via Ca2+/calmodulin-dependent release of the receptor complex from the neuronal cytoskeleton.</description><subject>Actinin - analysis</subject><subject>Animals</subject><subject>Binding Sites</subject><subject>Calcium - physiology</subject><subject>Calmodulin - physiology</subject><subject>Cell Line</subject><subject>Down-Regulation</subject><subject>Feedback</subject><subject>Infusions, Parenteral</subject><subject>Ion Channel Gating</subject><subject>Mutagenesis, Site-Directed</subject><subject>Neuronal Plasticity - physiology</subject><subject>Point Mutation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</subject><subject>Signal Transduction - physiology</subject><issn>0896-6273</issn><issn>1097-4199</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtLAzEUhYMotVZ_QmFWootoMjOZTFYirS9oFbRCdyFN7mBkXiaZQv-90wduXV2455x7uB9CY0puKKHZ7QfJRYazmCdXhFznhLEEL4_QkBLBcUqFOEbDP8spOvP-mxCaMkEHaCB4nIuYDdFiosqqMV1p62gOxqoAPup32nYVnkILtYE6RC-10sGuVbBNHTVF9IrnEL42JZ7ie98qF_pc9A4a2tA4f45OClV6uDjMEfp8fFhMnvHs7ellcj_DOhUkYJ7ENBEZZTzPCpNwliWMCa3zQmSZYMALrTRPqaEiJTzWOTPFSrEcckp4b0lG6HJ_t3XNTwc-yMp6DWWpamg6LylPRExp3BvZ3qhd472DQrbOVsptJCVyS1PuaMotKkmI3NGUyz43PhR0qwrMX-qAr9fv9jr0X64tOOm1hVr3IB3oIE1j_2n4BTkrg6k</recordid><startdate>19980801</startdate><enddate>19980801</enddate><creator>Zhang, Su</creator><creator>Ehlers, Michael D</creator><creator>Bernhardt, Jeffery P</creator><creator>Su, Ching-Tien</creator><creator>Huganir, Richard L</creator><general>Elsevier Inc</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>7TK</scope></search><sort><creationdate>19980801</creationdate><title>Calmodulin Mediates Calcium-Dependent Inactivation of N-Methyl-D-Aspartate Receptors</title><author>Zhang, Su ; Ehlers, Michael D ; Bernhardt, Jeffery P ; Su, Ching-Tien ; Huganir, Richard L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-732139615786fd37563559cc8f96695e7fcac741d194072c85dfba58e81079663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Actinin - analysis</topic><topic>Animals</topic><topic>Binding Sites</topic><topic>Calcium - physiology</topic><topic>Calmodulin - physiology</topic><topic>Cell Line</topic><topic>Down-Regulation</topic><topic>Feedback</topic><topic>Infusions, Parenteral</topic><topic>Ion Channel Gating</topic><topic>Mutagenesis, Site-Directed</topic><topic>Neuronal Plasticity - physiology</topic><topic>Point Mutation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</topic><topic>Signal Transduction - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Su</creatorcontrib><creatorcontrib>Ehlers, Michael D</creatorcontrib><creatorcontrib>Bernhardt, Jeffery P</creatorcontrib><creatorcontrib>Su, Ching-Tien</creatorcontrib><creatorcontrib>Huganir, Richard L</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>Neurosciences Abstracts</collection><jtitle>Neuron (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Su</au><au>Ehlers, Michael D</au><au>Bernhardt, Jeffery P</au><au>Su, Ching-Tien</au><au>Huganir, Richard L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Calmodulin Mediates Calcium-Dependent Inactivation of N-Methyl-D-Aspartate Receptors</atitle><jtitle>Neuron (Cambridge, Mass.)</jtitle><addtitle>Neuron</addtitle><date>1998-08-01</date><risdate>1998</risdate><volume>21</volume><issue>2</issue><spage>443</spage><epage>453</epage><pages>443-453</pages><issn>0896-6273</issn><eissn>1097-4199</eissn><abstract>Ca2+ influx through N-methyl-D-aspartate (NMDA) receptors activates signal transduction pathways critical for many forms of synaptic plasticity in the brain. NMDA receptor–mediated Ca2+ influx also downregulates the gating of NMDA channels through a process called Ca2+-dependent inactivation (CDI). Recent studies have demonstrated that the calcium binding protein calmodulin directly interacts with NMDA receptors, suggesting that calmodulin may play a role in CDI. We report here that the mutation of a specific calmodulin binding site in the C0 region of the NR1 subunit of the NMDA receptor blocks CDI. Moreover, intracellular infusion of a calmodulin inhibitory peptide markedly reduces CDI of both recombinant and neuronal NMDA receptors. Furthermore, this inactivating effect of calmodulin can be prevented by coexpressing a region of the cytoskeletal protein α-actinin2 known to interact with the C0 region of NR1. Taken together, these results demonstrate that the binding of Ca2+/calmodulin to NR1 mediates CDI of the NMDA receptor and suggest that inactivation occurs via Ca2+/calmodulin-dependent release of the receptor complex from the neuronal cytoskeleton.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>9728925</pmid><doi>10.1016/S0896-6273(00)80553-X</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0896-6273 |
| ispartof | Neuron (Cambridge, Mass.), 1998-08, Vol.21 (2), p.443-453 |
| issn | 0896-6273 1097-4199 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_17392112 |
| source | MEDLINE; Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; ScienceDirect Journals (5 years ago - present) |
| subjects | Actinin - analysis Animals Binding Sites Calcium - physiology Calmodulin - physiology Cell Line Down-Regulation Feedback Infusions, Parenteral Ion Channel Gating Mutagenesis, Site-Directed Neuronal Plasticity - physiology Point Mutation Rats Rats, Sprague-Dawley Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Signal Transduction - physiology |
| title | Calmodulin Mediates Calcium-Dependent Inactivation of N-Methyl-D-Aspartate Receptors |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T17%3A35%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Calmodulin%20Mediates%20Calcium-Dependent%20Inactivation%20of%20N-Methyl-D-Aspartate%20Receptors&rft.jtitle=Neuron%20(Cambridge,%20Mass.)&rft.au=Zhang,%20Su&rft.date=1998-08-01&rft.volume=21&rft.issue=2&rft.spage=443&rft.epage=453&rft.pages=443-453&rft.issn=0896-6273&rft.eissn=1097-4199&rft_id=info:doi/10.1016/S0896-6273(00)80553-X&rft_dat=%3Cproquest_cross%3E17392112%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=17392112&rft_id=info:pmid/9728925&rft_els_id=S089662730080553X&rfr_iscdi=true |