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Protein kinase A directly phosphorylates metabotropic glutamate receptor 5 to modulate its function
Author(s) -
Uematsu Ken,
Heiman Myriam,
Zelenina Marina,
Padovan Júlio,
Chait Brian T.,
Aperia Anita,
Nishi Akinori,
Greengard Paul
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13038
Subject(s) - metabotropic glutamate receptor 3 , metabotropic glutamate receptor 6 , metabotropic glutamate receptor 4 , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 5 , metabotropic glutamate receptor 7 , metabotropic glutamate receptor , metabotropic glutamate receptor 2 , chemistry , metabotropic glutamate receptor 8 , phosphorylation , microbiology and biotechnology , neuroscience , biochemistry , glutamate receptor , biology , receptor
Metabotropic glutamate receptor 5 ( mG luR5) 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 mG luR5 in a cAMP ‐ and PKA ‐dependent manner, suggesting that mG luR5 may be a direct target for PKA . Our study identifies mG luR5 at Ser870 as a direct substrate for PKA phosphorylation and demonstrates that this phosphorylation plays a critical role in the PKA ‐mediated modulation of mG luR5 functions such as extracellular signal‐regulated kinase phosphorylation and intracellular Ca 2+ oscillations. The identification of the molecular mechanism by which PKA signaling modulates mG luR5‐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.