RT Journal Article
SR Electronic
T1 Regulation of the NMDA Receptor Complex and Trafficking by Activity-Dependent Phosphorylation of the NR2B Subunit PDZ Ligand
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 10248
OP 10259
DO 10.1523/JNEUROSCI.0546-04.2004
VO 24
IS 45
A1 Hee Jung Chung
A1 Yan Hua Huang
A1 Lit-Fui Lau
A1 Richard L. Huganir
YR 2004
UL http://www.jneurosci.org/content/24/45/10248.abstract
AB Interactions between NMDA receptors (NMDARs) and the PDZ [postsynaptic density-95 (PSD-95)/Discs large/zona occludens-1] domains of PSD-95/SAP90 (synapse-associated protein with a molecular weight of 90 kDa) family proteins play important roles in the synaptic targeting and signaling of NMDARs. However, little is known about the mechanisms that regulate these PDZ domain-mediated interactions. Here we show that casein kinase II (CK2) phosphorylates the serine residue (Ser1480) within the C-terminal PDZ ligand (IESDV) of the NR2B subunit of NMDAR in vitro and in vivo. Phosphorylation of Ser1480 disrupts the interaction of NR2B with the PDZ domains of PSD-95 and SAP102 and decreases surface NR2B expression in neurons. Interestingly, activity of the NMDAR and Ca2+/calmodulin-dependent protein kinase II regulates CK2 phosphorylation of Ser1480. Furthermore, CK2 colocalizes with NR1 and PSD-95 at synaptic sites. These results indicate that activity-dependent CK2 phosphorylation of the NR2B PDZ ligand regulates the interaction of NMDAR with PSD-95/SAP90 family proteins as well as surface NMDAR expression and may be a critical mechanism for modulating excitatory synaptic function and plasticity.