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 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Activated CaMKII Couples GluN2B and Casein Kinase 2 to Control Synaptic NMDA Receptors. / Sanz-Clemente, Antonio; Gray, John; Ogilvie, Kyle A.; Nicoll, Roger A.; Roche, Katherine W.
In: Cell Reports, Vol. 3, No. 3, 2013, p. 607-614.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Activated CaMKII Couples GluN2B and Casein Kinase 2 to Control Synaptic NMDA Receptors
AU - Sanz-Clemente, Antonio
AU - Gray, John
AU - Ogilvie, Kyle A.
AU - Nicoll, Roger A.
AU - Roche, Katherine W.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84875808267&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2013.02.011
DO - 10.1016/j.celrep.2013.02.011
M3 - Article
VL - 3
SP - 607
EP - 614
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 3
ER -