Live imaging of endogenous Ca²⁺/calmodulin-dependent protein kinase II in neurons reveals that ischemia-related aggregation does not require kinase activity.

ABSTRACT: The Ca(2+) /calmodulin-dependent protein kinase II (CaMKII) forms 12meric holoenzymes. These holoenzymes cluster into larger aggregates within neurons under ischemic conditions and in vitro when ischemic conditions are mimicked. This aggregation is thought to be mediated by interaction between the regulatory domain of one kinase subunit with the T-site of another kinase subunit in a different holoenzyme, an interaction that requires stimulation by Ca(2+) /CaM and nucleotide for its induction. This model makes several predictions that were verified here: Aggregation in vitro was reduced by the CaMKII inhibitors tatCN21 and tatCN19o (which block the T-site) as well as by KN93 (which is CaM-competitive). Notably, these and previously tested manipulations that block CaMKII activation all reduc

SUBMITTER: Barcomb K 

PROVIDER: S-EPMC4636925 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature