Calmodulin-dependent protein kinase II. Multifunctional roles in neuronal differentiation and synaptic plasticity.
One of the most important mechanisms for regulating neuronal functions is through second messenger cascades that control protein kinases and the subsequent phosphorylation of substrate proteins. Ca2+/calmodulin-dependent protein kinase II (CaM-kinase II) is the most abundant protein kinase in mammalian brain tissues, and the alpha-subunit of this kinase is the major protein and enzymatic molecule of synaptic junctions in many brain regions. CaM-kinase II regulates itself through a complex autophosphorylation mechanism whereby it becomes calcium-independent following its initial activation. This property has implicated CaM-kinase II as a potential molecular switch at central nervous system (CNS) synapses. Recent studies have suggested that CaM-kinase II is involved in many diverse phenomena such as epilepsy, sensory deprivation, ischemia, synapse formation, synaptic transmission, long-term potentiation, learning, and memory. During brain development, the expression of CaM-kinase II at both protein and mRNA levels coincides with the active periods of synapse formation and, therefore, factors regulating the genes encoding kinase subunits may play a role in the cell-to-cell recognition events that underlie neuronal differentiation and the establishment of mature synaptic functions. Recent findings have demonstrated that the mRNA encoding the alpha-subunit of CaM-kinase II is localized in neuronal dendrites. Current speculation suggests that the localized translation of dendritic mRNAs encoding specific synaptic proteins may be responsible for producing synapse-specific changes associated with the processing, storage, and retrieval of information in neural networks.
Kelly
P T
PT
Department of Neurobiology and Anatomy, University of Texas Medical School, Houston.
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000254:growth & development; D002118:Calcium / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002454:Cell Differentiation / Q000502:physiology; D003712:Dendrites / Q000378:metabolism; D004789:Enzyme Activation; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015290:Second Messenger Systems; D013569:Synapses / Q000502:physiology
D012333:RNA, Messenger; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium