Postsynaptic Targeting of Protein Kinases and Phosphatases

Postsynaptic localization and regulation of AMPA receptors and Cav1.2 by β2 adrenergic receptor/PKA and Ca 2+ /CaMKII signaling

“…A key difference between signaling by NE-b 2 ARs-cAMP-PKA and by CaMKII is that the former is based on predetermined co-localization and co-assembly of all components except for NE, which is widely and diffusely released whereas CaMKII is evenly distributed throughout the dendritic shaft (Strack & Hell et al, 2008). However, stimulation of Ca 2+ influx through postsynaptic NMDARs will lead to recruitment of CaMKII to the stimulated spines as seen with ectopically expressed GFP-CaMKII (Shen & Meyer, 1999;Otmakhov et al, 2004;Rose et al, 2009) as well as endogenous CaMKII (Merrill et al, 2005;Strack & Hell et al, 2008). This recruitment depends on CaMKII binding to residues 1290-1310 in the C-terminus of GluN2B (Strack & Colbran, 1998;Leonard et al, 1999;Bayer et al, 2001;Halt et al, 2012).…”

CaMKII: Claiming Center Stage in Postsynaptic Function and Organization

“…Under basal conditions endogenous CaMKII appears to be enriched by a factor of ~2 in spines compared to dendritic shafts (Feng et al, 2011; Merrill et al, 2005; Strack and Hell, 2008). Under basal conditions, ~80% of CaMKII molecules exit spines and exchange with dendritic shaft CaMKII with a time constant between 1 and 5 min (~1s for free GFP) with ~ 15% remaining firmly anchored in spines after 30 min (Lee et al, 2009; Sharma et al, 2006; Sturgill et al, 2009).…”

“…Under basal conditions, ~80% of CaMKII molecules exit spines and exchange with dendritic shaft CaMKII with a time constant between 1 and 5 min (~1s for free GFP) with ~ 15% remaining firmly anchored in spines after 30 min (Lee et al, 2009; Sharma et al, 2006; Sturgill et al, 2009). Protein-protein interactions play a critical role in retaining CaMKII in spines, and F-actin, α-actinin, NMDARs and to some degree densin-180 are emerging as major CaMKII binding partners (Figure 2) (Strack and Hell, 2008). …”

“…Within seconds, perhaps milliseconds, of Ca 2+ influx, Ca 2+ /CaM will release CaMKII from F-actin and α-actinin for rapid relocation to the PSD. Within 1–2 min of Ca 2+ influx, redistribution of bulk CaMKII from shaft to spines also becomes obvious (Otmakhov et al, 2004; Shen and Meyer, 1999; Shen et al, 2000) (for endogenous CaMKII see (Ding et al, 2013; Merrill et al, 2005; Strack and Hell, 2008)). A two-step process is likely in place in which CaMKII will relocate to postsynaptic sites rather quickly from the spine interior and more slowly from shafts.…”

CaMKII binding to GluN2B is critical during memory consolidation

“…In general, learning, as well as LTP, requires both, Ca 2+ influx through the NMDAR (NMDA‐type glutamate receptor) and the ensuing CaMKII (calmodulin‐dependent protein kinase II) activation (Martin et al , 2000; Collingridge et al , 2004; Malenka and Bear, 2004; Kerchner and Nicoll, 2008; Lisman and Hell, 2008; Kessels and Malinow, 2009). Ca 2+ influx stimulates not only CaMKII activity but also CaMKII binding to the NMDAR (Strack and Colbran, 1998; Leonard et al , 1999; Bayer et al , 2006) and CaMKII accumulation at postsynaptic sites (Shen and Meyer, 1999; Bayer et al , 2006; Strack and Hell, 2008). This mechanism supports selective enrichment of CaMKII at synapses that are undergoing potentiation upon repeated glutamate uncaging, a model for LTP (Zhang et al , 2008; Lee et al , 2009).…”