title: Neuronal excitability and calcium/calmodulin-dependent protein kinase type II: location, location, location.
abstract: Calcium/calmodulin-dependent protein kinase type II (CaMKII) is a highly abundant serine/threonine kinase comprising a significant fraction of total protein in mammalian forebrain and forming a major component of the postsynaptic density. CaMKII is essential for certain forms of synaptic plasticity and memory consolidation and this is mediated through substrate binding and intramolecular phosphorylation of holoenzyme subunits. CaMKII is multifunctional; it targets a variety of cellular substrates, and this diversity depends on holoenzyme subunit composition. CaMKII comprises homooligomeric and heterooligomeric complexes generated from four subunits (α, β, δ, and γ) encoded by separate genes that are further expanded by extensive alternative splicing to more than 30 different isoforms. Much attention has been paid to understanding the regulation of CaMKII function through its structural diversity and/or substrate specificity. However, given the importance of subunit composition to holoenzyme activity, it is likely that specificity of cellular expression of CaMKII isoforms also plays a major role in regulation of enzyme function. Herein we review the cellular colocalization of CaMKII isoforms with special regard to the cell-type specificity of isoform expression in brain. In addition, we highlight the remarkable specificity of subcellular localization by the CaMKIIα isoform. In addition, we discuss the role that this cellular specificity of expression might play in propagating the type of recurrent neuronal activity associated with disorders such as temporal lobe epilepsy.
authors.affiliation: Center for Neuroscience, University of California-Davis, Davis, CA 95618, U.S.A.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Liu
authors.forename: Karl D
authors.initials: KD
authors.lastname: Murray
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000502:physiology*; D004827:Epilepsy / Q000201:enzymology / Q000503:physiopathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008854:Microscopy, Electron; D009457:Neuroglia / Q000201:enzymology / Q000502:physiology / Q000648:ultrastructure; D009474:Neurons / Q000201:enzymology* / Q000502:physiology* / Q000648:ultrastructure; D013347:Subcellular Fractions / Q000201:enzymology
chemical_list: D007527:Isoenzymes; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2