NMDA Receptor Activation Dephosphorylates AMPA Receptor Glutamate Receptor 1 Subunits at Threonine 840
| Autor: | Kimberly R Thompson, Erin E. Gray, Kelsey C. Martin, Thomas J. O'Dell, Seth G. N. Grant, Carrie L. Heusner, Marcelo P. Coba, Christopher N. G. Anderson, Jary Y. Delgado |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Threonine
inorganic chemicals Long-Term Potentiation Protein Array Analysis AMPA receptor In Vitro Techniques Biology Transfection Hippocampus Receptors N-Methyl-D-Aspartate Article Mice Animals Humans Protein phosphorylation Excitatory Amino Acid Agents Receptors AMPA Enzyme Inhibitors Protein kinase A Long-term depression Cells Cultured Neurons Analysis of Variance musculoskeletal neural and ocular physiology General Neuroscience Colforsin Isoproterenol Excitatory Postsynaptic Potentials Long-term potentiation Adrenergic beta-Agonists Interleukin-13 receptor Molecular biology Mice Inbred C57BL enzymes and coenzymes (carbohydrates) nervous system Mutagenesis Synaptic plasticity bacteria Phosphorylation |
| Zdroj: | The Journal of Neuroscience. 27:13210-13221 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.3056-07.2007 |
| Popis: | Phosphorylation-dependent changes in AMPA receptor function have a crucial role in activity-dependent forms of synaptic plasticity such as long-term potentiation (LTP) and long-term depression (LTD). Although three previously identified phosphorylation sites in AMPA receptor glutamate receptor 1 (GluR1) subunits (S818, S831, and S845) appear to have important roles in LTP and LTD, little is known about the role of other putative phosphorylation sites in GluR1. Here, we describe the characterization of a recently identified phosphorylation site in GluR1 at threonine 840. The results ofin vivoandin vitrophosphorylation assays suggest that T840 is not a substrate for protein kinases known to phosphorylate GluR1 at previously identified phosphorylation sites, such as protein kinase A, protein kinase C, and calcium/calmodulin-dependent kinase II. Instead,in vitrophosphorylation assays suggest that T840 is a substrate for p70S6 kinase. Although LTP-inducing patterns of synaptic stimulation had no effect on GluR1 phosphorylation at T840 in the hippocampal CA1 region, bath application of NMDA induced a strong, protein phosphatase 1- and/or 2A-mediated decrease in T840 phosphorylation. Moreover, GluR1 phosphorylation at T840 was transiently decreased by a chemical LTD induction protocol that induced a short-term depression of synaptic strength and persistently decreased by a chemical LTD induction protocol that induced a lasting depression of synaptic transmission. Together, our results show that GluR1 phosphorylation at T840 is regulated by NMDA receptor activation and suggest that decreases in GluR1 phosphorylation at T840 may have a role in LTD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|