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Allosteric Calcium Sensors in Synaptic Plasticity

About This Webinar

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 explain many properties of calmodulin by allosteric mechanisms, 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 in its different conformations, an allosteric model can explain how it can modulate different targets at different calcium concentrations. These 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. Allosteric models can be embedded in models of biochemical pathways to study the kinetics of responses to calcium. Finally, such models can be integrated with electrophysiological models at the level of the entire neuron.

Stefan M.I., Edelstein S.J., Le Novère N. (2008) An allosteric model of calmodulin explains differential activation of PP2B and CaMKII. Proceedings of the National Academy of Sciences USA, 105:10768-10773
Stefan M.I., Marshall D.P., Le Novère N. Structural analysis and stochastic modelling suggest a mechanism for calmodulin trapping by CaMKII. PLoS ONE (2012), 7(1): e29406
Li L., Stefan M.I., Le Novère N. Calcium input frequency, duration and amplitude differentially modulate the relative activation of calcineurin and CaMKII. PLoS ONE (2012), 7(9): e43810
Mattioni M., Le Novère N. Integration of biochemical and electrical signaling - multiscale model of the medium spiny neuron of the striatum. PLoS ONE (2013) 8(7): e66811
Lai M., Brun D., Edelstein S.J., Le Novère N. Modulation of calmodulin lobes by different targets: an allosteric model with hemiconcerted conformational transitions. PLoS Computational Biology (2015) 10(1):e0116616

Agenda
  • neurobiology
  • allosteric models
  • calcium sensors
  • neurobiology
  • modelling
Categories:
EDUCATION & LEARNING NONPROFITS & CAUSES SCIENCE & TECH
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Webinar Price: Free
Webinar ID: 26d06f5bcb13
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