Regulation of the NMDA receptor complex and trafficking by activity-dependent phosphorylation of the NR2B subunit PDZ ligand.
J Neurosci
; 24(45): 10248-59, 2004 Nov 10.
Article
en En
| MEDLINE
| ID: mdl-15537897
ABSTRACT
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.
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Banco de datos:
MEDLINE
Asunto principal:
Sinapsis
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Procesamiento Proteico-Postraduccional
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Receptores de N-Metil-D-Aspartato
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Transporte de Proteínas
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Quinasa de la Caseína II
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Proteínas del Tejido Nervioso
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Plasticidad Neuronal
Idioma:
En
Revista:
J Neurosci
Año:
2004
Tipo del documento:
Article
País de afiliación:
Estados Unidos