CaMKIIβ association with the actin cytoskeleton is regulated by alternative splicing

The Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII)beta has morphogenic functions in neurons not shared by the alpha isoform. CaMKII beta contains three exons (v1, v3, and v4) not present in the CaMKII alpha gene, and two of these exons (v1 and v4) are subject to differential alternative splicing. We show here that CaMKII beta, but not alpha, mediated bundling of F-actin filaments in vitro. Most importantly, inclusion of exon v1 was required for CaMKII beta association with the F-actin cytoskeleton within cells. CaMKII beta e, which is the dominant variant around birth and lacks exon v1 sequences, failed to associate with F-actin. By contrast, CaMKII beta', which instead lacks exon v4, associated with F-actin as full-length CaMKII beta. Previous studies with CaMKII beta mutants have indicated a role of nonstimulated kinase activity in enhancing dendritic arborization. Here, we show that F-actin-targeted CaMKII beta, but not alpha, was able to phosphorylate actin in vitro even by nonstimulated basal activity in absence of Ca2+/CaM. In rat pancreatic islets and in skeletal muscle, the actin-associated CaMKII beta' and beta M were the predominant variants, respectively. Thus, cytoskeletal targeting may mediate functions of CaMKII beta variants also outside the nervous system.