Neuronal excitability and calcium/calmodulin-dependent protein kinase type II: Location, location, location
Neuronal excitability and calcium/calmodulin-dependent protein kinase type II: Location, location, location
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DOI：
10.1111/j.1528-1167.2012.03474.x
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发表时间：
2012-06-01
期刊：
影响因子：
5.6
通讯作者：
Murray, Karl D.
中科院分区：
文献类型：
--
作者：
Liu, Xiao-Bo;Murray, Karl D.
钙/钙调蛋白依赖性蛋白激酶II（CaMKII）是一种高度丰富的丝氨酸/苏氨酸激酶，其在哺乳动物前脑中占总蛋白的很大一部分，并形成突触后密度的主要组分。CaMKII对于某些形式的突触可塑性和记忆巩固是必不可少的，这是通过底物结合和全酶亚基的分子内磷酸化介导的。CaMKII是多功能的;它靶向多种细胞底物，这种多样性取决于全酶亚基组成。CaMKII包括由四个亚基（a、β、d和？）由不同的基因编码，通过广泛的选择性剪接进一步扩展为30多种不同的同种型。人们已经注意到通过其结构多样性和/或底物特异性来理解CaMKII功能的调节。然而，考虑到亚基组成对全酶活性的重要性，CaMKII亚型的细胞表达的特异性也可能在酶功能的调节中起主要作用。在这里，我们回顾细胞共定位的CaMK Ⅱ亚型，特别是考虑到在大脑中的亚型表达的细胞类型特异性。此外，我们强调了CaMKIIa亚型的亚细胞定位的显着特异性。此外，我们还讨论了这种细胞特异性表达可能在传播与颞叶癫痫等疾病相关的复发性神经元活动类型中发挥的作用。
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 (a, beta, d, and ?) 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 CaMKIIa 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.