| First Author | Uematsu K | Year | 2015 |
| Journal | J Neurochem | Volume | 132 |
| Issue | 6 | Pages | 677-86 |
| PubMed ID | 25639954 | Mgi Jnum | J:220016 |
| Mgi Id | MGI:5632035 | Doi | 10.1111/jnc.13038 |
| Citation | Uematsu K, et al. (2015) Protein kinase A directly phosphorylates metabotropic glutamate receptor 5 to modulate its function. J Neurochem 132(6):677-86 |
| abstractText | 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(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(2+) oscillations. This study provides a direct molecular mechanism by which PKA signaling interacts with glutamate neurotransmission. |
