Title : Interactions between calmodulin and neurogranin govern the dynamics of CaMKII as a leaky integrator.

Pub. Date : 2020 Jul

PMID : 32678848






6 Functional Relationships(s)
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1 The scaffolding molecule, Ng, when present in significant concentration, limits the availability of free calmodulin (CaM), the protein which activates CaMKII in the presence of calcium. Calcium calcium/calmodulin dependent protein kinase II gamma Homo sapiens
2 We show that Ng plays an important modulatory role in CaMKII phosphorylation following a surge of high calcium concentration. Calcium calcium/calmodulin dependent protein kinase II gamma Homo sapiens
3 We find a non-intuitive dependence of this effect on CaM concentration that results from the different affinities of CaM for CaMKII depending on the number of calcium ions bound to the former. Calcium calcium/calmodulin dependent protein kinase II gamma Homo sapiens
4 We also study the effect of multiple calcium spikes on CaMKII holoenzyme autophosphorylation, and show that in the presence of phosphatase, CaMKII behaves as a leaky integrator of calcium signals, a result that has been recently observed in vivo. Calcium calcium/calmodulin dependent protein kinase II gamma Homo sapiens
5 We also study the effect of multiple calcium spikes on CaMKII holoenzyme autophosphorylation, and show that in the presence of phosphatase, CaMKII behaves as a leaky integrator of calcium signals, a result that has been recently observed in vivo. Calcium calcium/calmodulin dependent protein kinase II gamma Homo sapiens
6 Our models predict that the parameters of this leaky integrator are finely tuned through the interactions of Ng, CaM, CaMKII, and PP1, providing a mechanism to precisely control the sensitivity of synapses to calcium signals. Calcium calcium/calmodulin dependent protein kinase II gamma Homo sapiens