CaMKII Association with the Actin Cytoskeleton Is Regulated by Alternative Splicing□D

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