CaMKII binds activated NMDA receptor

Stable Identifier
R-HSA-445367
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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CaMKII can independentl bind to NMDA receptor-associated proteins alpha-actinin-2 (ACTN2) and densin-180 (LRRC7), as well as the NMDA receptor subunit GluN2B (GRIN2B, NR2B). Any of the four CAMK2 isoforms, CAMK2A, CAMK2B, CAMK2D or CAMK2G, which associate to form homomeric or heteromeric CaMKII dodecamers, can bind to ACTN2 and GluN2B, while LRRC7 shows the highest affinity for CAMK2A (Husi et al. 2000, Robison et al. 2005). Binding of CaMKII to the NMDA receptor-associated proteins is independent of CaMKII phosphorylation (Robinson et al. 2005), but phosphorylation of CaMKII on threonine residue T286 (T287 in CAMK2B, CAMK2D and CAMK2G) is needed for binding to GluN2B (Strack and Colbran 1998, Bayer et al. 2001). Binding to activated calmodulin is needed for translocation of CaMKII from the cytosol to the postsynaptic density (PSD). In the cytosol, CaMKII dodecamers containing CAMK2A subunit bind to F-actin. Dissociation of CAMK2A from F-actin requires either autophosphorylation of CAMK2A or binding to activated calmodulin (Shen and Meyer 1999).
Autophosphorylation increases the affinity of CaMKII for calmodulin and binding of CaMKII to the NMDA receptor subunit GluN2B locks the kinase in an active state, thus prolonging CaMKII signaling (Bayer et al. 2001). Prolonged activity of CaMKII is implicated in long-term potentiation (LTP), which is involved in learning and memory (Fukunaga et al. 1992, Otmakhov et al. 2004). Switching from GluN2B- to GluN2A (GRIN2A)-containing NDMA receptors results in reduced binding of CaMKII to PSD and reduced LTP, which may contribute to reduced synaptic plasticity (Barria and Malinow 2005).

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