CaMKIIbeta association with the actin cytoskeleton is regulated by alternative splicing.
The Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII)beta has morphogenic functions in neurons not shared by the alpha isoform. CaMKIIbeta contains three exons (v1, v3, and v4) not present in the CaMKIIalpha gene, and two of these exons (v1 and v4) are subject to differential alternative splicing. We show here that CaMKIIbeta, but not alpha, mediated bundling of F-actin filaments in vitro. Most importantly, inclusion of exon v1 was required for CaMKIIbeta association with the F-actin cytoskeleton within cells. CaMKIIbetae, which is the dominant variant around birth and lacks exon v1 sequences, failed to associate with F-actin. By contrast, CaMKIIbeta', which instead lacks exon v4, associated with F-actin as full-length CaMKIIbeta. Previous studies with CaMKIIbeta mutants have indicated a role of nonstimulated kinase activity in enhancing dendritic arborization. Here, we show that F-actin-targeted CaMKIIbeta, but not alpha, was able to phosphorylate actin in vitro even by nonstimulated basal activity in absence of Ca(2+)/CaM. In rat pancreatic islets and in skeletal muscle, the actin-associated CaMKIIbeta' and betaM were the predominant variants, respectively. Thus, cytoskeletal targeting may mediate functions of CaMKIIbeta variants also outside the nervous system.
O'Leary
Heather
H
Department of Pharmacology, Biomedical Sciences Program, and Neuroscience Program, University of Colorado Health Sciences Center, Aurora, CO 80045, USA.
Lasda
Erika
E
Bayer
K Ulrich
KU
D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism*; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D019556:COS Cells; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D002645:Chickens; D002522:Chlorocebus aethiops; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D007527:Isoenzymes / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; D007527:Isoenzymes; D050505:Mutant Proteins; D012333:RNA, Messenger; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases