N-methyl-D-aspartate receptors mediate the phosphorylation and desensitization of muscarinic receptors in cerebellar granule neurons
| Autor: | Sharad Mistry, Kenneth W. Young, Adrian J. Butcher, Ignacio Torrecilla, Andrew R. Bottrill, Kok Choi Kong, Andrew B. Tobin |
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| Přispěvatelé: | Butcher, Adrian [0000-0001-5723-8720], Apollo - University of Cambridge Repository |
| Rok vydání: | 2020 |
| Předmět: |
N-Methylaspartate
Recombinant Fusion Proteins Molecular Sequence Data Kainate receptor Class C GPCR Immune receptor Biology Phosphatidylinositols Biochemistry Receptors N-Methyl-D-Aspartate Rhodopsin-like receptors 03 medical and health sciences Mice 0302 clinical medicine Cerebellum Animals Amino Acid Sequence Calcium Signaling Phosphorylation Long-term depression Molecular Biology Cells Cultured 030304 developmental biology G protein-coupled receptor Feedback Physiological Mice Knockout Neurons Receptor Muscarinic M3 0303 health sciences Neuronal Plasticity 5-HT2 receptor Mechanisms of Signal Transduction Cell Biology Cell biology nervous system Calcium-Calmodulin-Dependent Protein Kinase Type 2 030217 neurology & neurosurgery Ion channel linked receptors Signal Transduction |
| Zdroj: | The Journal of Biological Chemistry |
| DOI: | 10.17863/cam.56540 |
| Popis: | Changes in synaptic strength mediated by ionotropic glutamate N-methyl-D-asparate (NMDA) receptors is generally considered to be the molecular mechanism underlying memory and learning. NMDA receptors themselves are subject to regulation through signaling pathways that are activated by G-protein-coupled receptors (GPCRs). In this study we investigate the ability of NMDA receptors to regulate the signaling of GPCRs by focusing on the G(q/11)-coupled M(3)-muscarinic receptor expressed endogenously in mouse cerebellar granule neurons. We show that NMDA receptor activation results in the phosphorylation and desensitization of M(3)-muscarinic receptors through a mechanism dependent on NMDA-mediated calcium influx and the activity of calcium-calmodulin-dependent protein kinase II. Our study reveals a complex pattern of regulation where GPCRs (M(3)-muscarinic) and NMDA receptors can feedback on each other in a process that is likely to influence the threshold value of signaling networks involved in synaptic plasticity. |
| Databáze: | OpenAIRE |
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