title: An ultrasensitive Ca2+/calmodulin-dependent protein kinase II-protein phosphatase 1 switch facilitates specificity in postsynaptic calcium signaling.
abstract: The strength of hippocampal synapses can be persistently increased by signals that activate Ca2+/calmodulin-dependent protein kinase II (CaMKII). This CaMKII-dependent long-term potentiation is important for hippocampal learning and memory. In this work we show that CaMKII exhibits an intriguing switch-like activation that likely is important for changes in synaptic strength. We found that autophosphorylation of CaMKII by itself showed a steep dependence on Ca2+ concentration [Hill coefficient (nH) approximately 5]. However, an even steeper Ca2+ dependence (nH approximately 8) was observed when autophosphorylation is balanced by the dephosphorylation activity of protein phosphatase 1 (PP1). This autophosphorylation-dephosphorylation switch was found to be reversible because PP1 dephosphorylates CaMKII when Ca2+ is lowered to a basal level. The switch-like response of a CaMKII-PP1 system suggests that CaMKII and PP1 may function together as a simple molecular device that specifically translates only strong Ca2+ signals into all-or-none potentiation of individual hippocampal synapses.
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA. michael.bradshaw@stanford.edu
authors.forename: J Michael
authors.initials: JM
authors.lastname: Bradshaw
authors.forename: Yoshi
authors.initials: Y
authors.lastname: Kubota
authors.forename: Tobias
authors.initials: T
authors.lastname: Meyer
authors.forename: Howard
authors.initials: H
authors.lastname: Schulman
mesh_terms: D020013:Calcium Signaling / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000502:physiology*; D010766:Phosphorylation; D054645:Protein Phosphatase 1; D013569:Synapses / Q000502:physiology*
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1