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Molecular Pharmacology

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Location-Dependent Signaling of the Group 1 Metabotropic Glutamate Receptor mGlu5

Yuh-Jiin I. Jong, Ismail Sergin, Carolyn A. Purgert and Karen L. O’Malley
Molecular Pharmacology December 2014, 86 (6) 774-785; DOI: https://doi.org/10.1124/mol.114.094763
Yuh-Jiin I. Jong
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri
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Ismail Sergin
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri
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Carolyn A. Purgert
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri
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Karen L. O’Malley
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri
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Abstract

Although G protein–coupled receptors are primarily known for converting extracellular signals into intracellular responses, some receptors, such as the group 1 metabotropic glutamate receptor, mGlu5, are also localized on intracellular membranes where they can mediate both overlapping and unique signaling effects. Thus, besides “ligand bias,” whereby a receptor’s signaling modality can shift from G protein dependence to independence, canonical mGlu5 receptor signaling can also be influenced by “location bias” (i.e., the particular membrane and/or cell type from which it signals). Because mGlu5 receptors play important roles in both normal development and in disorders such as Fragile X syndrome, autism, epilepsy, addiction, anxiety, schizophrenia, pain, dyskinesias, and melanoma, a large number of drugs are being developed to allosterically target this receptor. Therefore, it is critical to understand how such drugs might be affecting mGlu5 receptor function on different membranes and in different brain regions. Further elucidation of the site(s) of action of these drugs may determine which signal pathways mediate therapeutic efficacy.

Footnotes

    • Received July 15, 2014.
    • Accepted October 17, 2014.
  • This research was supported by the National Institutes of Health National Institute of Mental Health [Grants 1F30-MH091998-01, R01-MH57817, and R21-MH69646] and the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grant NS057105 (a Neuroscience Blueprint Core grant to Washington University)]. This work was also supported by FRAXA, the Simons Foundation, the Lilly Research Award Program, the McDonnell Center for Cellular and Molecular Neurobiology, and the Bakewell Family Foundation, as well as the Bioinformatics Core and Chemical Genetics Screening Core facilities at Washington University School of Medicine.

  • dx.doi.org/10.1124/mol.114.094763.

  • Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 86 (6)
Molecular Pharmacology
Vol. 86, Issue 6
1 Dec 2014
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Rapid CommunicationMinireviews

Intracellular mGlu5

Yuh-Jiin I. Jong, Ismail Sergin, Carolyn A. Purgert and Karen L. O’Malley
Molecular Pharmacology December 1, 2014, 86 (6) 774-785; DOI: https://doi.org/10.1124/mol.114.094763

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Rapid CommunicationMinireviews

Intracellular mGlu5

Yuh-Jiin I. Jong, Ismail Sergin, Carolyn A. Purgert and Karen L. O’Malley
Molecular Pharmacology December 1, 2014, 86 (6) 774-785; DOI: https://doi.org/10.1124/mol.114.094763
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    • Abstract
    • Introduction
    • General Features of mGlu5
    • Intracellular GPCRs
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    • Are There Other Intracellular mGlu Receptors?
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