Neurogranin stimulates Ca2+/calmodulin-dependent kinase II by suppressing calcineurin activity at specific calcium spike frequencies.

ABSTRACT: Calmodulin sits at the center of molecular mechanisms underlying learning and memory. Its complex and sometimes opposite influences, mediated via the binding to various proteins, are yet to be fully understood. Calcium/calmodulin-dependent protein kinase II (CaMKII) and calcineurin (CaN) both bind open calmodulin, favoring Long-Term Potentiation (LTP) or Depression (LTD) respectively. Neurogranin binds to the closed conformation of calmodulin and its impact on synaptic plasticity is less clear. We set up a mechanistic computational model based on allosteric principles to simulate calmodulin state transitions and its interactions with calcium ions and the three binding partners mentioned above. We simulated calcium spikes at various frequencies and show that neurogranin regulates synaptic p

SUBMITTER: Li L 

PROVIDER: S-EPMC7041932 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature