Mechanisms Associated with Activation of Intracellular Metabotropic Glutamate Receptor, mGluR5
Year: 2016
Type: article
Abstract: The group 1 metabotropic glutamate receptor, mGluR5, is found on the cell surface as well as on intracellular membranes where it can mediate both overlapping and unique signaling effects. Previously we have shown that glutamate activates intracellular mGluR5 by entry through sodium-dependent transporters and/or cystine glutamate exchangers. Calibrated antibody labelling suggests that the glutamate concentration within neurons is quite high (~10 mM) raising the question as to whether intracellular mGluR5 is maximally activated at all times or whether a different ligand might be responsible for receptor activation. To address this issue, we used cellular, optical and molecular techniques to show that intracellular glutamate is largely sequestered in mitochondria; that the glutamate concentration necessary to activate intracellular mGluR5 is about ten-fold higher than what is necessary to activate cell surface mGluR5; and uncaging caged glutamate within neurons can directly activate the receptor. Thus these studies further the concept that glutamate itself serves as the ligand for intracellular mGluR5.
Source: Neurochemical Research
Authors: Yuh-Jiin I. Jong, Karen L. O’Malley
Institution: Washington University in St. Louis
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,590
Funders: FRAXA Research Foundation, Simons Foundation, Eli Lilly and Company, National Institutes of Health, Intellectual and Developmental Disabilities Research Center, Center for Cellular Imaging, Washington University, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Intellectual and Developmental Disabilities Research Center, Washington University School of Medicine in St. Louis
Awards: G1599388212, LOCATION-DEPENDENT SIGNALING OF MGLU5 IN MODELS OF SYNAPTIC PLASTICITY USING CRISPR-TARGETED MICE, Washington University Center for Translational Neuroscience, G3802757361, G5138458822, WASHINGTON UNIVERSITY INTELLECTUAL AND DEVELOPMENTAL DISABILITIES RESEARCH CENTER, Metabotropic Receptors: Structure/Function/Regulation, G7605995353, G7860800203, G794885566, Signaling By Nuclear G-Protein Coupled Receptors, G9000175351, G9000239813, G9000282729
OpenAlex ID: W2486940235