Abstract
Long-term potentiation (LTP) of synaptic connections between neurons is a fundamental mechanism for learning and memory. In most synapses, highly abundant calmodulin-dependent protein kinase II (CaMKII) plays an essential role by linking large influxes of calcium to phosphorylation of ion channels embedded in the postsynaptic membrane. In addition to its enzymatic role, CaMKII accumulates in dendritic spines during LTP induction, where it establishes molecular interactions that maintain the synapse in a potentiated state. The aim of this project is to understand how CaMKII fulfils this poorly understood latter role by combining chemical, structural, physiological, and computational approaches.
References
1. Penny, C.P. & Gold, M.G. Mechanisms for localising calcineurin and CaMKII in dendritic spines. Cellular signalling (2018)
2. Walker-Gray, R., Stengel, F., Gold, M.G. Mechanisms for restraining cAMP-dependent protein kinase revealed by subunit quantitation and crosslinking approaches. PNAS, 114, 10414-10419 (2017)
3. Patel, N., Stengel, F., Aebersold, R., Gold, M.G. Molecular basis of AKAP79 regulation by calmodulin. Nature communications, 8, Article number 1681 (2017)
4. Ilangovan, A., Kay, C.W.M., Roier, S., El Mkami, H., Salvadori, E., Zechner, E.L., Zanetti, G., Waksman, G. Cryo-EM Structure of a Relaxase Reveals the Molecular Basis of DNA Unwinding during Bacterial Conjugation. Cell, 169, 708-721 (2017)