A model for molecular mechanisms of synaptic competition for a finite resource.
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) undergoes Ca(2+)/calmodulin-dependent autophosphorylation of threonine-286/287 (Thr(286/287)). Extremely high concentration of CaMKII in the postsynaptic spine indicates that increase in the Ca(2+) concentration in the spine induced by synaptic activation results in Thr(286/287) autophosphorylation of this enzyme. It has recently been shown that the K(d) value of CaMKII for Ca(2+)/calmodulin (Ca(2+)/CaM) drastically decreases after Thr(286/287) autophosphorylation. Therefore, Ca(2+)/CaM associated with CaMKII becomes tightly bound to this kinase after Thr(286/287) autophosphorylation. This has been called 'Ca(2+)/CaM trapping'. We discussed the functional significance of Ca(2+)/CaM trapping in the neuronal system by a mathematical-modelling approach. We considered neighbouring synapses formed on the same dendrite and different increase in the Ca(2+) concentration in each spine. CaMKII undergoing Thr(286/287) autophosphorylation in each spine is eager to recruit nearby calmodulin in the dendrite for Ca(2+)/CaM trapping. Since the amount of calmodulin is limited, recruiting calmodulin to each spine causes competition among synapses for this finite resource. The results of our computer simulation show that this competition leads to 'winner-take-all': almost all calmodulin is taken by a few synapses to which relatively large increases in the Ca(2+) concentration are assigned. These results suggest a novel form of synaptic encoding of information.
Okamoto
H
H
Corporate Research Labs., Fuji Xerox Co. Ltd., 430 Sakai, Nakai-machi, Ashigarakami-gun, Kanagawa, Japan. hiroshi.okamoto@fujixerox.co.jp
Ichikawa
K
K
D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D008959:Models, Neurological; D010766:Phosphorylation; D013569:Synapses / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*
D002147:Calmodulin; D002118:Calcium