Protein kinase CK2 in postsynaptic densities: Phosphorylation of PSD-95/SAP90 and NMDA receptor regulation

Dagoberto Soto, Floria Pancetti, Juan José Marengo, Mauricio Sandoval, Rodrigo Sandoval, Fernando Orrego, Ursula Wyneken

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Protein kinase CK2 (CK2) is highly expressed in rat forebrain where its function is not well understood. Subcellular distribution studies showed that the catalytic subunit of CK2 (CK2α) was enriched in postsynaptic densities (PSDs) by 68%. We studied the putative role of CK2 activity on N-methyl-d-aspartate receptor (NMDAR) function using isolated, patch-clamped PSDs in the presence of 2 mM extracellular Mg 2+. The usual activation by phosphorylation of the NMDARs in the presence of ATP was inhibited by the selective CK2 inhibitor 5,6-dichloro-1-β-ribofuranosyl benzimidazole (DRB). This inhibition was voltage-dependent, i.e., 100% at positive membrane potentials, while at negative potentials, inhibition was incomplete. Endogenous CK2 substrates were characterized by their ability to use GTP as a phosphoryl donor and susceptibility to inhibition by DRB. Immunoprecipitation assays and 2D gels indicated that PSD-95/SAP90, the NMDAR scaffolding protein, was a CK2 substrate, while the NR2A/B and NR1 NMDAR subunits were not. These results suggest that postsynaptic NMDAR regulation by CK2 is mediated by indirect mechanisms possibly involving PSD-95/SAP90.

Original languageEnglish
Pages (from-to)542-550
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume322
Issue number2
DOIs
StatePublished - 17 Sep 2004
Externally publishedYes

Bibliographical note

Funding Information:
We thank Professor Dr. Jorge Allende for helpful comments, and Fermelo for providing us with Amersham equipment. This work was supported by Fondecyt Project 1020257 and by Universidad de los Andes Projects.

Keywords

  • Excitatory neurotransmission
  • NMDA receptor
  • PSD-95/SAP90
  • Postsynaptic density
  • Protein kinase CK2
  • Rat forebrain

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