Activity-driven postsynaptic translocation of CaMKII.
Ca2+ influx through the NMDA receptor and subsequent activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) are crucial for learning and one of its physiological correlates, long-term potentiation (LTP). Ca2+/calmodulin promotes CaMKII binding to several postsynaptic proteins, including the NMDA receptor. These interactions strategically place CaMKII at locations where Ca2+ influx through the NMDA receptor is highest for further activation of CaMKII and for phosphorylation of nearby AMPA receptors and of other proteins that are important for LTP. Ca2+-dependent postsynaptic CaMKII clustering is of specific interest because LTP is synapse specific: only synapses that experience LTP-inducing high-frequency activity exhibit LTP. Ca2+-driven protein binding ensures that CaMKII accumulates only at those synapses undergoing LTP. This selectivity is economical and could contribute to the synapse specificity of LTP because downstream effects of CaMKII will occur mainly at synapses that accumulate CaMKII. In this article, we provide an overview of recent progress in postsynaptic CaMKII anchoring and discuss its implication in synaptic plasticity and the etiology and potential treatments of neurological diseases.
Merrill
Michelle A
MA
Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USA.
Chen
Yucui
Y
Strack
Stefan
S
Hell
Johannes W
JW
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology; D009422:Nervous System Diseases / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology; D011485:Protein Binding; D021381:Protein Transport; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases