Assemblies of calcium/calmodulin-dependent kinase II with actin and their dynamic regulation by calmodulin in dendritic spines

Qian Wang, Mingchen Chen, Nicholas P. Schafer, Carlos Bueno, Sarah S. Song, Andy Hudmon, Peter G. Wolynes, M. Neal Waxham, Margaret S. Cheung

Research output: Contribution to journalArticle

Abstract

Calcium/calmodulin-dependent kinase II (CaMKII) plays a key role in the plasticity of dendritic spines. Calcium signals cause calcium−calmodulin to activate CaMKII, which leads to remodeling of the actin filament (F-actin) network in the spine. We elucidate the mechanism of the remodeling by combining computer simulations with protein array experiments and electron microscopic imaging, to arrive at a structural model for the dodecameric complex of CaMKII with F-actin. The binding interface involves multiple domains of CaMKII. This structure explains the architecture of the micrometer-scale CaMKII/F-actin bundles arising from the multivalence of CaMKII. We also show that the regulatory domain of CaMKII may bind either calmodulin or F-actin, but not both. This frustration, along with the multipartite nature of the binding interface, allows calmodulin transiently to strip CaMKII from actin assemblies so that they can reorganize. This observation therefore provides a simple mechanism by which the structural dynamics of CaMKII establishes the link between calcium signaling and the morphological plasticity of dendritic spines.

Original languageEnglish (US)
Pages (from-to)18937-18942
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number38
DOIs
StatePublished - Sep 17 2019
Externally publishedYes

Fingerprint

Dendritic Spines
Calcium-Calmodulin-Dependent Protein Kinases
Calmodulin
Actins
Calcium
Protein Array Analysis
Frustration
Calcium Signaling
Structural Models
Actin Cytoskeleton
Computer Simulation
Spine
Electrons

Keywords

  • Actin remodeling
  • Calmodulin
  • CaMKII

ASJC Scopus subject areas

  • General

Cite this

Assemblies of calcium/calmodulin-dependent kinase II with actin and their dynamic regulation by calmodulin in dendritic spines. / Wang, Qian; Chen, Mingchen; Schafer, Nicholas P.; Bueno, Carlos; Song, Sarah S.; Hudmon, Andy; Wolynes, Peter G.; Neal Waxham, M.; Cheung, Margaret S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, No. 38, 17.09.2019, p. 18937-18942.

Research output: Contribution to journalArticle

Wang, Qian ; Chen, Mingchen ; Schafer, Nicholas P. ; Bueno, Carlos ; Song, Sarah S. ; Hudmon, Andy ; Wolynes, Peter G. ; Neal Waxham, M. ; Cheung, Margaret S. / Assemblies of calcium/calmodulin-dependent kinase II with actin and their dynamic regulation by calmodulin in dendritic spines. In: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; Vol. 116, No. 38. pp. 18937-18942.
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