Nuclear localization of functional metabotropic glutamate receptor mGlu1 in HEK293 cells and cortical neurons: role in nuclear calcium mobilization and development

• Published in: Journal of neurochemistry Vol. 101; no. 2; pp. 458 - 469
• Main Authors: Jong, Yuh‐Jiin I., Schwetye, Katherine E., O’Malley, Karen L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2007
• Subjects: Amino acids; Animals; Biochemistry; Calcium; Calcium - metabolism; Calcium Channels - pharmacology; Calcium Signaling - drug effects; Calcium Signaling - physiology; Cell Differentiation - physiology; Cell Line; Cell Nucleus - metabolism; Cells, Cultured; Cerebral Cortex - growth & development; Cerebral Cortex - metabolism; Cerebral Cortex - ultrastructure; cystine; Excitatory Amino Acid Agonists - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; excitatory amino acid transporter; glutamate exchanger; Humans; metabotropic glutamate receptor; Neurons; Neurons - drug effects; Neurons - metabolism; Neurosciences; Neurotransmitters; Rats; Rats, Sprague-Dawley; Receptors, Metabotropic Glutamate - agonists; Receptors, Metabotropic Glutamate - metabolism; Ryanodine Receptor Calcium Release Channel - drug effects; Ryanodine Receptor Calcium Release Channel - metabolism; Sodium Channels - drug effects; Sodium Channels - metabolism; Up-Regulation - physiology
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2006.04382.x

The Group I metabotropic glutamate receptor (mGlu1) plays an important role in neuromodulation, development, and synaptic plasticity. Using immunocytochemistry, subcellular fractionation, and western blot analysis, the present study shows that mGlu1a receptors are present on nuclear membranes in stably transfected human embryonic kidney 293 (HEK293) cells as well as being endogenously expressed on rat cortical nuclei. Both glutamate and the group I agonist, quisqualate, directly activate nuclear mGlu1 receptors leading to a characteristic oscillatory pattern of calcium flux in isolated HEK nuclei and a slow rise to plateau in isolated cortical nuclei. In either case calcium responses could be terminated upon application of the mGlu1‐selective antagonist, 7‐(hydroxyamino)cyclopropa[b]chromen‐1a‐carboxylate ethyl ester. Responses could also be blocked by ryanodine and inositol 1,4,5‐triphosphate receptor inhibitors, demonstrating the involvement of these calcium channels. Agonist activation of intracellular receptors was driven by Na+‐dependent and ‐independent processes in nuclei isolated from either HEK or cortical neurons. Finally, mGlu1 nuclear receptors were dramatically up‐regulated in the course of post‐natal development. Therefore, like the other Group I receptor, mGlu5, mGlu1 can function as an intracellular receptor, suggesting a more encompassing role for nuclear G protein‐coupled receptors and downstream signaling elements in the regulation of nuclear events.