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

Yin S, Noetzel MJ, Johnson KA, Zamorano R, Jalan-Sakrikar N, Gregory KJ, Conn PJ, Niswender CM
J Neurosci. 2014 34 (1): 79-94

PMID: 24381270 · PMCID: PMC3866496 · DOI:10.1523/JNEUROSCI.1129-13.2014

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.

MeSH Terms (17)

Allosteric Regulation Animals Brain Cells, Cultured Central Nervous System Excitatory Amino Acid Agonists Excitatory Amino Acid Antagonists Female HEK293 Cells Humans Male Mice Mice, Inbred ICR Protein Multimerization Rats Rats, Sprague-Dawley Receptors, Metabotropic Glutamate

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