Light-dependent inhibition of CaMKII

Murakoshi, H. et al. Neuron 94, 37–47 (2017).

Ca²⁺/calmodulin kinase II (CaMKII) plays a central role in synaptic plasticity. While the temporal requirements for CaMKII activation have been addressed by pharmacological inhibition, such measurements are not precise, as delays occur during bath application of these compounds. Murakoshi et al. report a genetically encoded and light-dependent inhibitor for CaMKII. The researchers fused an inhibitory peptide, the autocamtide inhibitory peptide 2 (AIP2), to LOV2-Jα, a domain that changes its conformation from closed to open in response to blue light, thus creating a photoactivatable CaMKII inhibitor. They applied this inhibitor, called paAIP2, to determine the precise temporal window in which CaMKII is required to exert its function during long-term potentiation in rat hippocampal slice preparations and in mice during a behavioral task.