Protein kinase A directly phosphorylates metabotropic glutamate receptor 5 to modulate its function
| Autor: | Myriam Heiman, Ken Uematsu, Julio C. Padovan, Akinori Nishi, Marina Zelenina, Anita Aperia, Brian T. Chait, Paul Greengard |
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| Přispěvatelé: | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Heiman, Myriam |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
animal diseases
Receptor Metabotropic Glutamate 5 Mitogen-activated protein kinase kinase Biology Biochemistry Article MAP2K7 Cellular and Molecular Neuroscience Mice Organ Culture Techniques mental disorders Animals Humans ASK1 Amino Acid Sequence Phosphorylation Protein kinase A Mice Knockout Binding Sites MAP kinase kinase kinase Metabotropic glutamate receptor 5 Metabotropic glutamate receptor 4 Metabotropic glutamate receptor 6 Cyclic AMP-Dependent Protein Kinases Cell biology Mice Inbred C57BL HEK293 Cells nervous system |
| Zdroj: | PMC |
| Popis: | Metabotropic glutamate receptor 5 (mGluR5) regulates excitatory post-synaptic signaling in the central nervous system (CNS) and is implicated in various CNS disorders. Protein kinase A (PKA) signaling is known to play a critical role in neuropsychiatric disorders such as Parkinson's disease, schizophrenia, and addiction. Dopamine signaling is known to modulate the properties of mGluR5 in a cAMP- and PKA-dependent manner, suggesting that mGluR5 may be a direct target for PKA. Our study identifies mGluR5 at Ser870 as a direct substrate for PKA phosphorylation and demonstrates that this phosphorylation plays a critical role in the PKA-mediated modulation of mGluR5 functions such as extracellular signal-regulated kinase phosphorylation and intracellular Ca[superscript 2+] oscillations. The identification of the molecular mechanism by which PKA signaling modulates mGluR5-mediated cellular responses contributes to the understanding of the interaction between dopaminergic and glutamatergic neuronal signaling. We identified serine residue 870 (S870) in metabotropic glutamate receptor 5 (mGluR5) as a direct substrate for protein kinase A (PKA). The phosphorylation of this site regulates the ability of mGluR5 to induce extracellular signal-regulated kinase (ERK) phosphorylation and intracellular Ca[superscript 2+] oscillations. This study provides a direct molecular mechanism by which PKA signaling interacts with glutamate neurotransmission. |
| Databáze: | OpenAIRE |
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