Abstract
Most common forms of short-term synaptic plasticities are associated with non-linear responses to calcium increases in the post-synaptic compartment. Calmodulin, one of the main calcium sensors in eukaryotic cells, is a small protein that carries four calcium binding sites with different affinities.
One can extend the allosteric framework to explain the properties of calmodulin, and in particular the apparent increasing calcium affinity with fractional occupancy, the activity of non-saturated forms of calmodulin, and the increase in calcium affinity once calmodulin is bound to a target. Because calmodulin can bind several targets with different affinities, the allosteric model can explain that it can be used to implement changeover switches, where it can modulate different targets at different calcium concentrations. In particular, allosteric properties of calmodulin may suffice to explain the differential activation of calcineurin, leading to synaptic long-term depression, and calcium/calmodulin kinase II, leading to synaptic long term potentiation, a molecular basis of learning and memory. However, to properly understand the effect of calmodulin requires to take into account its concentration. As for most signalling systems in vivo, the concentrations of calmodulin are near the values of the calcium dissociation constants. Increasingly strong ligand depletions progressively increase the dynamic range, that is the range of concentrations “measured” by the system, and decreases the actual cooperativity of calcium binding.
More information on Nick’s work is available here
Refreshments will be served following the seminar