Loading…

Selective actions of novel allosteric modulators reveal functional heteromers of metabotropic glutamate receptors in the CNS

Metabotropic glutamate (mGlu) receptors play important roles in regulating CNS function and are known to function as obligatory dimers. Although recent studies have suggested heterodimeric assembly of mGlu receptors in vitro, the demonstration that distinct mGlu receptor proteins can form heterodime...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of neuroscience 2014-01, Vol.34 (1), p.79-94
Main Authors: Yin, Shen, Noetzel, Meredith J, Johnson, Kari A, Zamorano, Rocio, Jalan-Sakrikar, Nidhi, Gregory, Karen J, Conn, P Jeffrey, Niswender, Colleen M
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c447t-c4a050db0942dc680d244b81443c8f02e378a6d6c4de16ede0b51cc26b2c26903
cites cdi_FETCH-LOGICAL-c447t-c4a050db0942dc680d244b81443c8f02e378a6d6c4de16ede0b51cc26b2c26903
container_end_page 94
container_issue 1
container_start_page 79
container_title The Journal of neuroscience
container_volume 34
creator Yin, Shen
Noetzel, Meredith J
Johnson, Kari A
Zamorano, Rocio
Jalan-Sakrikar, Nidhi
Gregory, Karen J
Conn, P Jeffrey
Niswender, Colleen M
description Metabotropic glutamate (mGlu) receptors play important roles in regulating CNS function and are known to function as obligatory dimers. Although recent studies have suggested heterodimeric assembly of mGlu receptors in vitro, the demonstration that distinct mGlu receptor proteins can form heterodimers or hetero-complexes with other mGlu subunits in native tissues, such as neurons, has not been shown. Using biochemical and pharmacological approaches, we demonstrate here that mGlu2 and mGlu4 form a hetero-complex in native rat and mouse tissues which exhibits a distinct pharmacological profile. These data greatly extend our current understanding of mGlu receptor interaction and function and provide compelling evidence that mGlu receptors can function as heteromers in intact brain circuits.
doi_str_mv 10.1523/JNEUROSCI.1129-13.2014
format article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3866496</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1827920097</sourcerecordid><originalsourceid>FETCH-LOGICAL-c447t-c4a050db0942dc680d244b81443c8f02e378a6d6c4de16ede0b51cc26b2c26903</originalsourceid><addsrcrecordid>eNqFkV9rFDEUxYModlv9CiWPvsz25s8mMy-CLFUrpQXXPodM5k53JDNZk8yC4Ic3u62LPvlyb-Cc3-GGQ8glgyVbcXH15e764ev9Zn2zZIw3FRNLDky-IIuiNhWXwF6SBXANlZJanpHzlL4DgAamX5MzLkXNirggvzbo0eVhj9SWFaZEQ0-nsEdPrfchZYyDo2PoZm9ziIlG3KP1tJ-no788t1hMYcR4ZEfMtg05hl3hHv2c7WgzFszh7hgwTDRvka7vNm_Iq976hG-f9wV5-Hj9bf25ur3_dLP-cFs5KXUu08IKuhYayTunaui4lG3NpBSu7oGj0LVVnXKyQ6awQ2hXzDmuWl5GA-KCvH_K3c3tiJ3DKUfrzS4Oo40_TbCD-VeZhq15DHsjaqVko0rAu-eAGH7MmLIZh-TQezthmJNhNdcNB2j0_62yAV0uZwererK6GFKK2J8uYmAOLZtTy-bQsmHCHFou4OXf_zlhf2oVvwEgxaff</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1490744317</pqid></control><display><type>article</type><title>Selective actions of novel allosteric modulators reveal functional heteromers of metabotropic glutamate receptors in the CNS</title><source>PubMed Central</source><creator>Yin, Shen ; Noetzel, Meredith J ; Johnson, Kari A ; Zamorano, Rocio ; Jalan-Sakrikar, Nidhi ; Gregory, Karen J ; Conn, P Jeffrey ; Niswender, Colleen M</creator><creatorcontrib>Yin, Shen ; Noetzel, Meredith J ; Johnson, Kari A ; Zamorano, Rocio ; Jalan-Sakrikar, Nidhi ; Gregory, Karen J ; Conn, P Jeffrey ; Niswender, Colleen M</creatorcontrib><description>Metabotropic glutamate (mGlu) receptors play important roles in regulating CNS function and are known to function as obligatory dimers. Although recent studies have suggested heterodimeric assembly of mGlu receptors in vitro, the demonstration that distinct mGlu receptor proteins can form heterodimers or hetero-complexes with other mGlu subunits in native tissues, such as neurons, has not been shown. Using biochemical and pharmacological approaches, we demonstrate here that mGlu2 and mGlu4 form a hetero-complex in native rat and mouse tissues which exhibits a distinct pharmacological profile. These data greatly extend our current understanding of mGlu receptor interaction and function and provide compelling evidence that mGlu receptors can function as heteromers in intact brain circuits.</description><identifier>ISSN: 0270-6474</identifier><identifier>EISSN: 1529-2401</identifier><identifier>DOI: 10.1523/JNEUROSCI.1129-13.2014</identifier><identifier>PMID: 24381270</identifier><language>eng</language><publisher>United States: Society for Neuroscience</publisher><subject>Allosteric Regulation - drug effects ; Allosteric Regulation - physiology ; Animals ; Brain - drug effects ; Brain - physiology ; Cells, Cultured ; Central Nervous System - drug effects ; Central Nervous System - physiology ; Excitatory Amino Acid Agonists - chemistry ; Excitatory Amino Acid Agonists - pharmacology ; Excitatory Amino Acid Antagonists - chemistry ; Excitatory Amino Acid Antagonists - pharmacology ; Female ; HEK293 Cells ; Humans ; Male ; Mice ; Mice, Inbred ICR ; Protein Multimerization ; Rats ; Rats, Sprague-Dawley ; Receptors, Metabotropic Glutamate - agonists ; Receptors, Metabotropic Glutamate - antagonists &amp; inhibitors ; Receptors, Metabotropic Glutamate - chemistry ; Receptors, Metabotropic Glutamate - physiology</subject><ispartof>The Journal of neuroscience, 2014-01, Vol.34 (1), p.79-94</ispartof><rights>Copyright © 2014 the authors 0270-6474/14/340079-16$15.00/0 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c447t-c4a050db0942dc680d244b81443c8f02e378a6d6c4de16ede0b51cc26b2c26903</citedby><cites>FETCH-LOGICAL-c447t-c4a050db0942dc680d244b81443c8f02e378a6d6c4de16ede0b51cc26b2c26903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866496/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866496/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24381270$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yin, Shen</creatorcontrib><creatorcontrib>Noetzel, Meredith J</creatorcontrib><creatorcontrib>Johnson, Kari A</creatorcontrib><creatorcontrib>Zamorano, Rocio</creatorcontrib><creatorcontrib>Jalan-Sakrikar, Nidhi</creatorcontrib><creatorcontrib>Gregory, Karen J</creatorcontrib><creatorcontrib>Conn, P Jeffrey</creatorcontrib><creatorcontrib>Niswender, Colleen M</creatorcontrib><title>Selective actions of novel allosteric modulators reveal functional heteromers of metabotropic glutamate receptors in the CNS</title><title>The Journal of neuroscience</title><addtitle>J Neurosci</addtitle><description>Metabotropic glutamate (mGlu) receptors play important roles in regulating CNS function and are known to function as obligatory dimers. Although recent studies have suggested heterodimeric assembly of mGlu receptors in vitro, the demonstration that distinct mGlu receptor proteins can form heterodimers or hetero-complexes with other mGlu subunits in native tissues, such as neurons, has not been shown. Using biochemical and pharmacological approaches, we demonstrate here that mGlu2 and mGlu4 form a hetero-complex in native rat and mouse tissues which exhibits a distinct pharmacological profile. These data greatly extend our current understanding of mGlu receptor interaction and function and provide compelling evidence that mGlu receptors can function as heteromers in intact brain circuits.</description><subject>Allosteric Regulation - drug effects</subject><subject>Allosteric Regulation - physiology</subject><subject>Animals</subject><subject>Brain - drug effects</subject><subject>Brain - physiology</subject><subject>Cells, Cultured</subject><subject>Central Nervous System - drug effects</subject><subject>Central Nervous System - physiology</subject><subject>Excitatory Amino Acid Agonists - chemistry</subject><subject>Excitatory Amino Acid Agonists - pharmacology</subject><subject>Excitatory Amino Acid Antagonists - chemistry</subject><subject>Excitatory Amino Acid Antagonists - pharmacology</subject><subject>Female</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred ICR</subject><subject>Protein Multimerization</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Metabotropic Glutamate - agonists</subject><subject>Receptors, Metabotropic Glutamate - antagonists &amp; inhibitors</subject><subject>Receptors, Metabotropic Glutamate - chemistry</subject><subject>Receptors, Metabotropic Glutamate - physiology</subject><issn>0270-6474</issn><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNqFkV9rFDEUxYModlv9CiWPvsz25s8mMy-CLFUrpQXXPodM5k53JDNZk8yC4Ic3u62LPvlyb-Cc3-GGQ8glgyVbcXH15e764ev9Zn2zZIw3FRNLDky-IIuiNhWXwF6SBXANlZJanpHzlL4DgAamX5MzLkXNirggvzbo0eVhj9SWFaZEQ0-nsEdPrfchZYyDo2PoZm9ziIlG3KP1tJ-no788t1hMYcR4ZEfMtg05hl3hHv2c7WgzFszh7hgwTDRvka7vNm_Iq976hG-f9wV5-Hj9bf25ur3_dLP-cFs5KXUu08IKuhYayTunaui4lG3NpBSu7oGj0LVVnXKyQ6awQ2hXzDmuWl5GA-KCvH_K3c3tiJ3DKUfrzS4Oo40_TbCD-VeZhq15DHsjaqVko0rAu-eAGH7MmLIZh-TQezthmJNhNdcNB2j0_62yAV0uZwererK6GFKK2J8uYmAOLZtTy-bQsmHCHFou4OXf_zlhf2oVvwEgxaff</recordid><startdate>20140101</startdate><enddate>20140101</enddate><creator>Yin, Shen</creator><creator>Noetzel, Meredith J</creator><creator>Johnson, Kari A</creator><creator>Zamorano, Rocio</creator><creator>Jalan-Sakrikar, Nidhi</creator><creator>Gregory, Karen J</creator><creator>Conn, P Jeffrey</creator><creator>Niswender, Colleen M</creator><general>Society for Neuroscience</general><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>7X8</scope><scope>7TK</scope><scope>5PM</scope></search><sort><creationdate>20140101</creationdate><title>Selective actions of novel allosteric modulators reveal functional heteromers of metabotropic glutamate receptors in the CNS</title><author>Yin, Shen ; Noetzel, Meredith J ; Johnson, Kari A ; Zamorano, Rocio ; Jalan-Sakrikar, Nidhi ; Gregory, Karen J ; Conn, P Jeffrey ; Niswender, Colleen M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c447t-c4a050db0942dc680d244b81443c8f02e378a6d6c4de16ede0b51cc26b2c26903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Allosteric Regulation - drug effects</topic><topic>Allosteric Regulation - physiology</topic><topic>Animals</topic><topic>Brain - drug effects</topic><topic>Brain - physiology</topic><topic>Cells, Cultured</topic><topic>Central Nervous System - drug effects</topic><topic>Central Nervous System - physiology</topic><topic>Excitatory Amino Acid Agonists - chemistry</topic><topic>Excitatory Amino Acid Agonists - pharmacology</topic><topic>Excitatory Amino Acid Antagonists - chemistry</topic><topic>Excitatory Amino Acid Antagonists - pharmacology</topic><topic>Female</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred ICR</topic><topic>Protein Multimerization</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Metabotropic Glutamate - agonists</topic><topic>Receptors, Metabotropic Glutamate - antagonists &amp; inhibitors</topic><topic>Receptors, Metabotropic Glutamate - chemistry</topic><topic>Receptors, Metabotropic Glutamate - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yin, Shen</creatorcontrib><creatorcontrib>Noetzel, Meredith J</creatorcontrib><creatorcontrib>Johnson, Kari A</creatorcontrib><creatorcontrib>Zamorano, Rocio</creatorcontrib><creatorcontrib>Jalan-Sakrikar, Nidhi</creatorcontrib><creatorcontrib>Gregory, Karen J</creatorcontrib><creatorcontrib>Conn, P Jeffrey</creatorcontrib><creatorcontrib>Niswender, Colleen M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yin, Shen</au><au>Noetzel, Meredith J</au><au>Johnson, Kari A</au><au>Zamorano, Rocio</au><au>Jalan-Sakrikar, Nidhi</au><au>Gregory, Karen J</au><au>Conn, P Jeffrey</au><au>Niswender, Colleen M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Selective actions of novel allosteric modulators reveal functional heteromers of metabotropic glutamate receptors in the CNS</atitle><jtitle>The Journal of neuroscience</jtitle><addtitle>J Neurosci</addtitle><date>2014-01-01</date><risdate>2014</risdate><volume>34</volume><issue>1</issue><spage>79</spage><epage>94</epage><pages>79-94</pages><issn>0270-6474</issn><eissn>1529-2401</eissn><abstract>Metabotropic glutamate (mGlu) receptors play important roles in regulating CNS function and are known to function as obligatory dimers. Although recent studies have suggested heterodimeric assembly of mGlu receptors in vitro, the demonstration that distinct mGlu receptor proteins can form heterodimers or hetero-complexes with other mGlu subunits in native tissues, such as neurons, has not been shown. Using biochemical and pharmacological approaches, we demonstrate here that mGlu2 and mGlu4 form a hetero-complex in native rat and mouse tissues which exhibits a distinct pharmacological profile. These data greatly extend our current understanding of mGlu receptor interaction and function and provide compelling evidence that mGlu receptors can function as heteromers in intact brain circuits.</abstract><cop>United States</cop><pub>Society for Neuroscience</pub><pmid>24381270</pmid><doi>10.1523/JNEUROSCI.1129-13.2014</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0270-6474
ispartof The Journal of neuroscience, 2014-01, Vol.34 (1), p.79-94
issn 0270-6474
1529-2401
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3866496
source PubMed Central
subjects Allosteric Regulation - drug effects
Allosteric Regulation - physiology
Animals
Brain - drug effects
Brain - physiology
Cells, Cultured
Central Nervous System - drug effects
Central Nervous System - physiology
Excitatory Amino Acid Agonists - chemistry
Excitatory Amino Acid Agonists - pharmacology
Excitatory Amino Acid Antagonists - chemistry
Excitatory Amino Acid Antagonists - pharmacology
Female
HEK293 Cells
Humans
Male
Mice
Mice, Inbred ICR
Protein Multimerization
Rats
Rats, Sprague-Dawley
Receptors, Metabotropic Glutamate - agonists
Receptors, Metabotropic Glutamate - antagonists & inhibitors
Receptors, Metabotropic Glutamate - chemistry
Receptors, Metabotropic Glutamate - physiology
title Selective actions of novel allosteric modulators reveal functional heteromers of metabotropic glutamate receptors in the CNS
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T17%3A16%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Selective%20actions%20of%20novel%20allosteric%20modulators%20reveal%20functional%20heteromers%20of%20metabotropic%20glutamate%20receptors%20in%20the%20CNS&rft.jtitle=The%20Journal%20of%20neuroscience&rft.au=Yin,%20Shen&rft.date=2014-01-01&rft.volume=34&rft.issue=1&rft.spage=79&rft.epage=94&rft.pages=79-94&rft.issn=0270-6474&rft.eissn=1529-2401&rft_id=info:doi/10.1523/JNEUROSCI.1129-13.2014&rft_dat=%3Cproquest_pubme%3E1827920097%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c447t-c4a050db0942dc680d244b81443c8f02e378a6d6c4de16ede0b51cc26b2c26903%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1490744317&rft_id=info:pmid/24381270&rfr_iscdi=true