CaMKII Isoforms in Learning and Memory: Localization and Function

ZALCMAN, GISELA; FEDERMAN, NOEL; ROMANO, ARTURO

Frontiers in Molecular Neuroscience

Frontiers

Año: 2018 vol. 11 p. 1 - 14

CaMKII is one of the main effectors enzymes involved in calcium signaling in eukaryotic cells.The enzyme is activated as a result of increased intracellular calcium and phosphorylates targetproteins involved in various processes such as mobilization of synaptic vesicles, modulation ofion channels, regulation of gene expression, regulation of muscle contraction, and LTP (Wu andMcMurray, 2001; Lisman et al., 2012; Ojuka et al., 2012). Over the last two decades CaMKII hasbecome one of the most studied proteins in the nervous system, and it has proven to be a key protein involved in learning, memory, and synaptic plasticity (Lisman et al., 2002, 2012; Irvineet al., 2006; Lucchesi et al., 2011; Coultrap and Bayer, 2012). CaMKII is a holoenzyme composedof 12 subunits of 56?60 kDa that are assembled into 2 rings of 6 subunits each (Gaertner et al.,2004). Interestingly, these subunits are proteins encoded by four distinct but highly related genestermedcamk2a,camk2b,camk2d, andcamk2g, which give rise to four different CaMKII isoforms:α,β,δ, andγ. Each isoform has different calcium trapping kinetics, sub-cellular localization andaffinity for other protein binding, thus enabling CaMKII to have different properties according toits subunit composition, which can be composed of a single type or a combination of isoforms(Srinivasan et al., 1994; Brocke et al., 1999). Furthermore, the RNAs that code for the differentisoforms can undergo alternative splicing, resulting in the synthesis of approximately 30 differentvariants (Hudmon and Schulman, 2002). In the present review, we will first describe generalfeatures of CaMKII structure and mechanism of activation and then summarize the main featuresof each isoform and their splicing variants as well as our current understanding on their rolein learning and memory. Studies focused on the interplay between subunit composition andfunctional outcome will not only contribute to understand why CaMKII is so fundamental forlearning and memory processes but they might also reveal key information on the molecular mechanisms involved in memory storage