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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...
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Published in: | The Journal of neuroscience 2014-01, Vol.34 (1), p.79-94 |
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container_title | The Journal of neuroscience |
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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 |
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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. 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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 |
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