βCaMKII regulates actin assembly and structure

Hugo Sanabria, Matthew T. Swulius, Steven J. Kolodziej, Jun Liu, M. Neal Waxham

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Ca2+-Calmodulin-dependent protein kinase II (CaMKII) is an abundant synaptic protein that was recently shown to regulate the organization of actin filaments leading to structural modifications of synapses. CaMKII is a dodecameric complex with a special architecture that provides it with unique potential for organizing the actin cytoskeleton.Wereport using biochemical assays that the β isoform of CaMKII binds to and bundles actin filaments, and the disposition ofβCaMKII within the actin bundles was revealed by cryoelectron tomography. In addition, βCaMKII was found to inhibit actin polymerization, suggesting that it either serves as a capping protein or binds monomeric actin, reducing the amount of freely available monomers to nucleate polymer assembly. By means of fluorescent cross-correlation spectroscopy, we determined that βCaMKII does indeed bind to monomeric actin, reaching saturation at a stoichiometry of 12:1 actin monomers per βCaMKII holoenzyme with a binding constant of 2.4 × 105 M-1. In cells, βCaMKII has a dual functional role; it can sequester monomeric actin to reduce actin polymerization and can also bundle actin filaments. Together, these effects would impact both the dynamics of actin filament assembly and enhance the rigidity of the filaments once formed, significantly impacting the structure of synapses.

Original languageEnglish (US)
Pages (from-to)9770-9780
Number of pages11
JournalJournal of Biological Chemistry
Volume284
Issue number15
DOIs
StatePublished - Apr 10 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Sanabria, H., Swulius, M. T., Kolodziej, S. J., Liu, J., & Waxham, M. N. (2009). βCaMKII regulates actin assembly and structure. Journal of Biological Chemistry, 284(15), 9770-9780. https://doi.org/10.1074/jbc.M809518200