Protein kinase A directly phosphorylates metabotropic glutamate receptor 5 to modulate its function
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Heiman_Protein kinase.pdf
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Author(s)
Uematsu, Ken
Heiman, Myriam
Zelenina, Marina
Padovan, Julio
Chait, Brian T.
Aperia, Anita
Nishi, Akinori
Greengard, Paul
Date Issued
March 2015
Journal
Journal of Neurochemistry
Publisher
Wiley Blackwell
Citation
Uematsu, Ken, Myriam Heiman, Marina Zelenina, Julio Padovan, Brian T. Chait, Anita Aperia, Akinori Nishi, and Paul Greengard. “Protein Kinase A Directly Phosphorylates Metabotropic Glutamate Receptor 5 to Modulate Its Function.” Journal of Neurochemistry 132, no. 6 (March 2015): 677–686.
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Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
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DOI of Published Version
https://doi.org/10.1111/jnc.13038
