Calcium/calmodulin-dependent protein kinase II: an unforgettable kinase.

The search for “memory molecules” and why CaMKII is an appealing candidate Since the time neuroscientists first recognized that biochemical events inside neurons could influence the function of the brain, there have been people looking for “memory molecules.” This elusive ion, small molecule, protein, or nucleic acid would be the keystone on which memory was built; understanding the memory molecule would allow us to unlock the mysteries of cognition. Models of how this molecule could work abounded, but the idea of a memory molecule as a kinase/phosphatase-based molecular switch emerged as an important contender (Lisman, 1985). The discovery that there actually was an abundant neuronal protein kinase that had switch-like properties (Miller and Kennedy, 1986) was met with great enthusiasm, and the role of calcium/ calmodulin-dependent protein kinase II (CaMKII) in learning and memory has been studied intensively. This series of reviews will cover recent advances in our understanding of the regulation of CaMKII and its autophosphorylation by phosphatases and localizing interactions, its involvement in synaptic plasticity, and the advent of mammalian genetic models for the study of CaMKII in behavior.