Calcium/Calmodulin-dependent protein kinase II (CaMKII), a second messengermediated kinase, is one of the most abundant proteins in the brain, as it accounts for up to 2% of total protein, depending on the brain region1, 2. It was first discovered as the Synapsin I kinase, indicating that the protein was located presynaptically and involved in neurotransmitter release3, 4. However, subsequent studies showed that this kinase was also present at the postsynaptic site5, 6 where it is enriched in the postsynaptic density (PSD)7-9. The CaMKII family consists of four different isozymes, α, β, γ and δ, each encoded by a separate gene. The first CaMKII isozymes discovered were α- and βCaMKII4, 10, which form holoenzymes consisting of 12 subunits1. Later the two other isozymes were described (γ and δ), which are much less prominent in the brain11, 12. Even though the different isozymes are encoded by different genes, they are highly homologous in their domain organization (as reviewed by13). They all contain a catalytic, an autoregulatory and an association domain (fig 1). The autoregulatory domain, containing several autophosphorylation sites, is highly conserved in all isozymes. The differences between the proteins are found in the association domain, where variable insertions reside or splicing can occur. All isozymes also have different subtypes (e.g. β’ and βΜ, or αΒ) due to alternative splicing in the association domain.

CaMKII, proteins, synaptic plasticity
Y. Elgersma (Ype)
Erasmus University Rotterdam
Netherlands Organisation for Scientific Research, Neuro-BSIK, The European Communit, PrinsesBeatrix Fonds, Hersenstichting Nederland, Netherlands Epilepsy Fund, Angelman Syndrome Foundation (ASF)
Erasmus MC: University Medical Center Rotterdam

van Woerden, G.M. (2009, December 2). Role of CaMKII in Synaptic Plasticity, Learning and Disease. Erasmus University Rotterdam. Retrieved from