title: Sequences within the C Terminus of the Metabotropic Glutamate Receptor 5 (mGluR5) Are Responsible for Inner Nuclear Membrane Localization.
abstract: Traditionally, G-protein-coupled receptors (GPCR) are thought to be located on the cell surface where they transmit extracellular signals to the cytoplasm. However, recent studies indicate that some GPCRs are also localized to various subcellular compartments such as the nucleus where they appear required for various biological functions. For example, the metabotropic glutamate receptor 5 (mGluR5) is concentrated at the inner nuclear membrane (INM) where it mediates Ca2+changes in the nucleoplasm by coupling with Gq/11Here, we identified a region within the C-terminal domain (amino acids 852-876) that is necessary and sufficient for INM localization of the receptor. Because these sequences do not correspond to known nuclear localization signal motifs, they represent a new motif for INM trafficking. mGluR5 is also trafficked to the plasma membrane where it undergoes re-cycling/degradation in a separate receptor pool, one that does not interact with the nuclear mGluR5 pool. Finally, our data suggest that once at the INM, mGluR5 is stably retained via interactions with chromatin. Thus, mGluR5 is perfectly positioned to regulate nucleoplasmic Ca2+in situ.
authors.affiliation: From the Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Ismail
authors.initials: I
authors.lastname: Sergin
authors.affiliation: From the Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Yuh-Jiin I
authors.initials: YI
authors.lastname: Jong
authors.affiliation: From the Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Harmon
authors.affiliation: From the Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Vikas
authors.initials: V
authors.lastname: Kumar
authors.affiliation: From the Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri 63110 omalleyk@wustl.edu.
authors.forename: Karen L
authors.initials: KL
authors.lastname: O'Malley
mesh_terms: D021581:Active Transport, Cell Nucleus; D020816:Amino Acid Motifs; D000818:Animals; D002118:Calcium / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry; D003342:Corpus Striatum / Q000166:cytology; D003593:Cytoplasm / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D005971:Glutamates / Q000737:chemistry; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D009474:Neurons / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism*; D019913:Nuclear Localization Signals; D000072417:Protein Domains; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5 / Q000737:chemistry*
chemical_list: D002843:Chromatin; C578935:GRM5 protein, human; D005971:Glutamates; D019913:Nuclear Localization Signals; D064529:Receptor, Metabotropic Glutamate 5; D002118:Calcium
keywords: G-protein-coupled receptor (GPCR); calcium; chromatin; glutamate; metabotropic glutamate receptor (mGluR); nuclear membrane; nuclear transport