The Ca++/calmodulin-dependent protein kinase II (CaMKII) is a major mediator of Ca++ signals in a variety of cells. This enzyme exists in especially high quantities in hippocampus and cortex and has been shown to affect dendritic arborization, synapse density, and synaptic plasticity. The α-isoform has been extensively studied and is known to play a role in learning and memory, but we know much less about the β-isoform. While the α-isoform lacks the ability to bind F-actin, the β-isoform does bind to F-actin and also undergoes much more extensive alternative splicing. The β-isoform can also regulate dendritic arborization, while the α-isoform does not. Variants of the β-isoform are also the predominant forms of CaMKII expressed in muscle (βM) and pancreatic β-cells (βΔ3). The functional consequences of this regulated alternative splicing are not known. The purpose of this investigation was (1) to examine which regions of β-CaMKII are important for F-actin binding and (2) to see how β-CaMKII splice variants differ in their effects on neuron morphogenesis and subcellular localization. More specifically, effects on dendritic arborization and CaMKII/F-actin interactions were examined using designed mutant constructs and splice variants expressed in hippocampal neurons. It was found that alternative splicing can affect both dendritic arborization and subcellular localization of the enzyme. Also, the regions of CaMKII that may be involved in actin-binding functions and dendritic arborization were further elucidated. The ability of splice variants to bind F-actin did not appear to correlate directly with their ability to increase dendritic arborization. These results may better help describe the role of CaMKII in learning and memory. Furthermore, since β-CaMKII has been shown to have some role in the release of secretory granules in pancreatic β-cells, an understanding of the function of both mutant constructs and splice variants may help establish the etiology of some forms of diabetes and, in the future, provide possible avenues for new therapeutic interventions.
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