Studying CaMKII: Tools and standards

The Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) is a ubiquitous mediator of cellular Ca2+ signals with both enzymatic and structural functions. Here, we briefly introduce the complex regulation of CaMKII and then provide a comprehensive overview of the expanding toolbox to study CaMKII. Beyond a variety of distinct mutants, these tools now include optical methods for measurement and manipulation, with the latter including light-induced inhibition, stimulation, and sequestration. Perhaps most importantly, there are now three mechanistically distinct classes of specific CaMKII inhibitors, and their combined use enables the interrogation of CaMKII functions in a manner that is powerful and sophisticated yet also accessible. This review aims to provide guidelines for the interpretation of the results obtained with these tools, with careful consideration of their direct and indirect effects. Brown and Bayer review and provide a guide for the use of tools to study CaMKII and the interpretation of the results, specifically covering pharmacological inhibitors that now include three classes of mechanistically distinct inhibitors that can be readily used also by the non-specialist.