PT  - JOURNAL ARTICLE
AU  - Yuh-Jiin I Jong
AU  - Ismail Sergin
AU  - Carolyn A Purgert
AU  - Karen L O'Malley
TI  - Location-dependent Signaling of the Group 1 Metabotropic Glutamate Receptor, mGlu5.
AID  - 10.1124/mol.114.094763
DP  - 2014 Oct 17
TA  - Molecular Pharmacology
PG  - mol.114.094763
4099  - http://molpharm.aspetjournals.org/content/early/2014/10/17/mol.114.094763.short
4100  - http://molpharm.aspetjournals.org/content/early/2014/10/17/mol.114.094763.full
AB  - Although GPCRs 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 signaling can also be influenced by "location bias", that is the particular membrane and/or cell type from which it signals. Because mGlu5 plays important roles in both normal development and in disorders such as Fragile X, 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 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.