title: Selective actions of novel allosteric modulators reveal functional heteromers of metabotropic glutamate receptors in the CNS.
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.
authors.affiliation: Department of Pharmacology and the Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee 37232, and Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
authors.forename: Shen
authors.initials: S
authors.lastname: Yin
authors.forename: Meredith J
authors.initials: MJ
authors.lastname: Noetzel
authors.forename: Kari A
authors.initials: KA
authors.lastname: Johnson
authors.forename: Rocio
authors.initials: R
authors.lastname: Zamorano
authors.forename: Nidhi
authors.initials: N
authors.lastname: Jalan-Sakrikar
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Gregory
authors.forename: P Jeffrey
authors.initials: PJ
authors.lastname: Conn
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Niswender
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000737:chemistry / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D055503:Protein Multimerization; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C108823:metabotropic glutamate receptor 4