Abstract
Synaptic activity triggers a profound reorganization of the molecular composition of excitatory synapses. For example, NMDA receptors are removed from synapses in an activity- and calcium-dependent manner, via casein kinase 2 (CK2) phosphorylation of the PDZ ligand of the GluN2B subunit (S1480). However, how synaptic activity drives this process remains unclear because CK2 is a constitutively active kinase, which is not directly regulated by calcium. We show here that activated CaMKII couples GluN2B and CK2 to form a trimolecular complex and increases CK2-mediated phosphorylation of GluN2B S1480. In addition, a GluN2B mutant, which contains an insert to mimic the GluN2A sequence and cannot bind to CaMKII, displays reduced S1480 phosphorylation and increased surface expression. We find that although disrupting GluN2B/CaMKII binding reduces synapse number, it increases synaptic-GluN2B content. Therefore, the GluN2B/CaMKII association controls synapse density and PSD composition in an activity-dependent manner, including recruitment of CK2 for the removal of GluN2B from synapses.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 607-614 |
| Number of pages | 8 |
| Journal | Cell reports |
| Volume | 3 |
| Issue number | 3 |
| DOIs | |
| State | Published - 2013 |
Funding
We thank John D. Badger II for technical assistance. We also thank the NINDS sequencing facility and light imaging facility for expertise and advice. This research was supported by the NINDS Intramural Research Program (A.S.-C., K.A.O., and K.W.R.) and grants from the NIMH (J.A.G. and R.A.N.). J.A.G. is funded by a NARSAD Young Investigator Award and is the NARSAD Hammerschlag Family Investigator.
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology