@article {Murphy869, author = {Jessica A. Murphy and Ivar S. Stein and C. Geoffrey Lau and Rui T. Peixoto and Teresa K. Aman and Naoki Kaneko and Kelly Aromolaran and Jessica L. Saulnier and Gabriela K. Popescu and Bernardo L. Sabatini and Johannes W. Hell and R. Suzanne Zukin}, title = {Phosphorylation of Ser1166 on GluN2B by PKA Is Critical to Synaptic NMDA Receptor Function and Ca2+ Signaling in Spines}, volume = {34}, number = {3}, pages = {869--879}, year = {2014}, doi = {10.1523/JNEUROSCI.4538-13.2014}, publisher = {Society for Neuroscience}, abstract = {The NMDA-type glutamate receptor (NMDAR) is essential for synaptogenesis, synaptic plasticity, and higher cognitive function. Emerging evidence indicates that NMDAR Ca2+ permeability is under the control of cAMP/protein kinase A (PKA) signaling. Whereas the functional impact of PKA on NMDAR-dependent Ca2+ signaling is well established, the molecular target remains unknown. Here we identify serine residue 1166 (Ser1166) in the carboxy-terminal tail of the NMDAR subunit GluN2B to be a direct molecular and functional target of PKA phosphorylation critical to NMDAR-dependent Ca2+ permeation and Ca2+ signaling in spines. Activation of β-adrenergic and D1/D5-dopamine receptors induces Ser1166 phosphorylation. Loss of this single phosphorylation site abolishes PKA-dependent potentiation of NMDAR Ca2+ permeation, synaptic currents, and Ca2+ rises in dendritic spines. We further show that adverse experience in the form of forced swim, but not exposure to fox urine, elicits striking phosphorylation of Ser1166 in vivo, indicating differential impact of different forms of stress. Our data identify a novel molecular and functional target of PKA essential to NMDAR-mediated Ca2+ signaling at synapses and regulated by the emotional response to stress.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/34/3/869}, eprint = {https://www.jneurosci.org/content/34/3/869.full.pdf}, journal = {Journal of Neuroscience} }