Sequences within the C Terminus of the Metabotropic Glutamate Receptor 5 (mGluR5) Are Responsible for Inner Nuclear Membrane Localization
Year: 2017
Type: article
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 Ca 2+ changes in the nucleoplasm by coupling with G q/11 . Here, 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 Ca 2+ in situ .
Source: Journal of Biological Chemistry
Institution: Washington University in St. Louis
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Awards: LOCATION-DEPENDENT SIGNALING OF MGLU5 IN MODELS OF SYNAPTIC PLASTICITY USING CRISPR-TARGETED MICE, SELECTIVE ACTIONS OF MGLU5 RECEPTOR NEGATIVE ALLOSTERIC MODULATORS, Expanding Access to Planar Illumination Microscopy in a Neuroimaging Core, G6024414047, Metabotropic Receptors: Structure/Function/Regulation, MECHANISMS UNDERLYING INTRACELLULAR MGLUR5 ROLE IN NOCICEPTION, Signaling By Nuclear G-Protein Coupled Receptors
OpenAlex ID: W2572498644