Calcium-calmodulin-dependent protein kinase II isoforms differentially impact the dynamics and structure of the actin cytoskeleton.
Calcium-calmodulin-dependent protein kinase II (CaMKII) has been implicated in a wide variety of cellular processes, which include a critical regulatory role in actin cytoskeletal assembly. CaMKII is ubiquitous in cells, expressed as one of four isoforms termed α, β, γ, and δ. Characterization of the CaMKII-actin interaction has mainly focused on the β isoform, which has been shown to bundle actin filaments and sequester actin monomers in an activity-dependent manner. Much less is known about the interactions of other CaMKII isoforms with actin. In this work, isoform specific interactions of CaMKII with actin are described and reveal that the δ isoform of CaMKII bundles F-actin filaments like the β isoform while the γ isoform induces a novel layered structure in filaments. Using electron tomography, CaMKII holoenzymes are clearly identified in the complexes bridging the actin filaments, allowing direct visualization of the interactions between CaMKII isoforms and actin. In addition, we determined the isoform specificity of CaMKII-mediated inhibition of actin polymerization and discovered that all isoforms inhibit polymerization to varying degrees: β > γ ≈ δ > α (from most to least effective). Ca(2+)/CaM activation of all kinase isoforms produced a robust increase in actin polymerization that surpassed the rates of polymerization in the absence of kinase inhibition. These results indicate that diversity exists between the types of CaMKII-actin interactions mediated by the different isoforms and that the CaMKII isoform composition differentially impacts the formation and maintenance of the actin cytoskeleton.
The Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, 6431 Fannin Street, Houston, TX 77030, USA.
Laurel
L
Hoffman
Madeline M
MM
Farley
M Neal
MN
Waxham
D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure*; D000199:Actins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000737:chemistry / Q000378:metabolism*; D058105:Polymerization; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism
D000199:Actins; D020033:Protein Isoforms; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2