Multifunctional calcium and calmodulin-dependent kinase II in neuronal function and disease

The brain is highly specialized to carry out complex signaling and intracellular information processing. To accomplish this task, neurons possess a vast array of signaling effecters, receptors and second messenger systems. Calcium is a major second messenger in neurons and plays a critical role in signal transduction and the regulation of many neuronal functions (Daw et al., 1993; Pulvirenti, 1992; Bar et al., 1990; Celio, 1989). Upon entering neurons, calcium ions encounter many proteins that moderate its biochemical effects. These proteins include proteases, kinases, phosphatases and transcription regulators. Protein phosphorylation is a major neuronal effector system that controls many neuronal calcium-regulated processes. These processes include neurotransmitter synthesis and release (Nichols et al., 1990; Griffith and Schulman, 1988; Nose et al., 1985; Isobe et al., 1991), synaptic vesicle mobilization (DeLorenzo, 1982; Burke and DeLorenzo, 1982; Prey et al., 1995; Llinas et al., 1985), cytoskeletal dynamics (Goldenring et al., 1984; Burke and DeLorenzo, 1981, 1982; Schulman, 1993) and ion conductances (Sakakibara er al., 1986; Anderson et al., 1994; Baskys et al., 1990). Many dedicated and multifunctional kinases have been identified in brain tissue. This review will focus on the multifunctional calcium and calmodulin-dependent protein kinase type II (CaM kinase II). CaM kinase II is a neuronally enriched, Ca2+-regulated signal transducing enzyme that modulates many of the above neuronal functions.