Bayer, K. U. & Schulman, H. CaM kinase: still inspiring at 40. Neuron 103, 380–394 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yasuda, R., Hayashi, Y. & Hell, J. W. CaMKII: a central molecular organizer of synaptic plasticity, learning and memory. Nat. Rev. Neurosci. https://doi.org/10.1038/s41583-022-00624-2 (2022).

Article  PubMed  Google Scholar 

Lisman, J., Yasuda, R. & Raghavachari, S. Mechanisms of CaMKII action in long-term potentiation. Nat. Rev. Neurosci. 13, 169–182 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Coultrap, S. J. & Bayer, K. U. CaMKII regulation in information processing and storage. Trends Neurosci. 35, 607–618 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tullis, J. E. et al. LTP induction by structural rather than enzymatic functions of CaMKII. Nature 621, 146–153 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bayer, K. U., De Koninck, P., Leonard, A. S., Hell, J. W. & Schulman, H. Interaction with the NMDA receptor locks CaMKII in an active conformation. Nature 411, 801–805 (2001).

Article  CAS  PubMed  Google Scholar 

Giese, K. P., Fedorov, N. B., Filipkowski, R. K. & Silva, A. J. Autophosphorylation at Thr286 of the alpha calcium-calmodulin kinase II in LTP and learning. Science 279, 870–873 (1998).

Article  CAS  PubMed  Google Scholar 

Chen, X. et al. CaMKII autophosphorylation is the only enzymatic event required for synaptic memory. Proc. Natl Acad. Sci. USA 121, e2402783121 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rumian, N. L. et al. LTP expression mediated by autonomous activity of GluN2B-bound CaMKII. Cell Rep. https://doi.org/10.1016/j.celrep.2024.114866 (2024).

Irvine, E. E., Vernon, J. & Giese, K. P. AlphaCaMKII autophosphorylation contributes to rapid learning but is not necessary for memory. Nat. Neurosci. 8, 411–412 (2005).

Article  CAS  PubMed  Google Scholar 

Rossetti, T. et al. Memory erasure experiments indicate a critical role of CaMKII in memory storage. Neuron 96, 207–216 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xiao, K., Li, Y., Chitwood, R. A. & Magee, J. C. A critical role for CaMKII in behavioral timescale synaptic plasticity in hippocampal CA1 pyramidal neurons. Sci. Adv. 9, eadi3088 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jain, A. et al. Dendritic, delayed, stochastic CaMKII activation in behavioural time scale plasticity. Nature https://www.nature.com/articles/s41586-024-08021-8 (2024).

Tombes, R. M., Faison, M. O. & Turbeville, J. M. Organization and evolution of multifunctional Ca2+/CaM-dependent protein kinase genes. Gene 322, 17–31 (2003).

Article  CAS  PubMed  Google Scholar 

Erondu, N. E. & Kennedy, M. B. Regional distribution of type II Ca2+/calmodulin-dependent protein kinase in rat brain. J. Neurosci. 5, 3270–3277 (1985).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, X., Zhang, C., Szabo, G. & Sun, Q. Q. Distribution of CaMKIIα expression in the brain in vivo, studied by CaMKIIα-GFP mice. Brain Res. 1518, 9–25 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Silva, A. J., Paylor, R., Wehner, J. M. & Tonegawa, S. Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice. Science 257, 206–211 (1992).

Article  CAS  PubMed  Google Scholar 

Silva, A. J., Stevens, C. F., Tonegawa, S. & Wang, Y. Deficient hippocampal long-term potentiation in alpha-calcium-calmodulin kinase II mutant mice. Science 257, 201–206 (1992).

Article  CAS  PubMed  Google Scholar 

Chao, L. H. et al. A mechanism for tunable autoinhibition in the structure of a human Ca2+/calmodulin-dependent kinase II holoenzyme. Cell 146, 732–745 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sloutsky, R. et al. Heterogeneity in human hippocampal CaMKII transcripts reveals allosteric hub-dependent regulation. Sci Signal. https://doi.org/10.1126/scisignal.aaz0240 (2020).

Buonarati, O. R., Miller, A. P., Coultrap, S. J., Bayer, K. U. & Reichow, S. L. Conserved and divergent features of neuronal CaMKII holoenzyme structure, function, and high-order assembly. Cell Rep. 37, 110168 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Myers, J. B. et al. The CaMKII holoenzyme structure in activation-competent conformations. Nat. Commun. 8, 15742 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hanson, P. I., Meyer, T., Stryer, L. & Schulman, H. Dual role of calmodulin in autophosphorylation of multifunctional CaM kinase may underlie decoding of calcium signals. Neuron 12, 943–956 (1994).

Article  CAS  PubMed  Google Scholar 

Rich, R. C. & Schulman, H. Substrate-directed function of calmodulin in autophosphorylation of Ca2+/calmodulin-dependent protein kinase II. J. Biol. Chem. 273, 28424–28429 (1998).

Article  CAS  PubMed  Google Scholar 

Saneyoshi, T. et al. Reciprocal activation within a kinase-effector complex underlying persistence of structural LTP. Neuron 102, 1199–1210 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jiao, Y. et al. Characterization of a central Ca2+/calmodulin-dependent protein kinase IIalpha/beta binding domain in densin that selectively modulates glutamate receptor subunit phosphorylation. J. Biol. Chem. 286, 24806–24818 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Magupalli, V. G. et al. Ca2+-independent activation of Ca2+/calmodulin-dependent protein kinase II bound to the C-terminal domain of CaV2.1 calcium channels. J. Biol. Chem. 288, 4637–4648 (2013).

Article  CAS  PubMed  Google Scholar 

Hudmon, A. et al. CaMKII tethers to L-type Ca2+ channels, establishing a local and dedicated integrator of Ca2+ signals for facilitation. J. Cell Biol. 171, 537–547 (2005).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, X. et al. A novel mechanism for Ca2+/calmodulin-dependent protein kinase II targeting to L-type Ca2+ channels that initiates long-range signaling to the nucleus. J. Biol. Chem. 292, 17324–17336 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bayer, K. U. et al. Transition from reversible to persistent binding of CaMKII to postsynaptic sites and NR2B. J. Neurosci. 26, 1164–1174 (2006).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ozden, C. et al. CaMKII binds both substrates and activators at the active site. Cell Rep. 40, 111064 (2022).

Article  CAS  PubMed  PubMed Central