CAM KINASE AUTOREGULATION AND ROLE IN SYNAPTIC FUNCTION

描述（研究者摘要）：本研究的长期目标 就是定义记忆的分子基础 为了实现这一目标， 将使用简化的方法，并假设学习 脊椎动物神经元中的记忆是由分子启动和表达的， 突触可塑性（synaptic plasticity） 许多蛋白质需要形成 功能性突触 申请人专注于一个最 丰富的钙调素激酶。 钙调素激酶高度集中在 突触前和突触后元件，在那里它构成了一个大的 分离的突触后密度的蛋白质的百分比（40%）。 当神经元活动允许Ca++-内流进入神经元时，CaM激酶被激活。 细胞内区室，无论是从外部或内部Ca++商店。 当激活时，CaM激酶磷酸化几种神经元蛋白质 控制各种功能。 有趣的是，CaM激酶也 自身磷酸化（autophosphorylation）。 自磷酸化变化 CaM激酶转化为不再需要Ca++内流的酶， 活动，并在简单的理论意义上“记住”过去的活动 通过记录自磷酸化的量中的Ca++-内流， 钙调素激酶。 这种活动可以在一段时间内表达 在Ca++浓度恢复到静息水平之后。 Ca++戏剧 在许多形式的短期和长期神经元可塑性中起重要作用， 这被认为是学习和记忆的细胞基础。 的 申请人一直在研究Ca++活化蛋白激酶的作用 (e.g.,钙调素激酶）在海马脑片细胞学习模型中的作用 长时程增强（LTP） 初步实验表明， 钙调素激酶在细胞凋亡的诱导过程中起着某种迄今未知的作用。 LTP

DESCRIPTION (Investigator's Abstract): The long-term goal of this research is to define the molecular basis of memory. To accomplish this goal a reductionist approach will be used and the assumption is made that learning and memory in vertebrate neurons is initiated and expressed by molecules at synapses (synaptic plasticity). Numerous proteins are required to form functional synapses. The applicant has concentrated on one of the most abundant, CaM-kinase. CaM-kinase is highly concentrated at both presynaptic and postsynaptic elements where it constitutes a large percentage of the protein (40 percent) of isolated postsynaptic densities. CaM-kinase is activated when neuronal activity permits Ca++-influx into the intracellular compartment, either from external or internal Ca++ stores. When activated, CaM-kinase phosphorylates several neuronal proteins controlling a variety of functions. Interestingly, CaM-kinase also phosphorylates itself (autophosphorylation). Autophosphorylation changes CaM-kinase into an enzyme which no longer requires Ca++-influx for activity, and in a simple theoretical sense "remembers" the past activity of the synapse by recording Ca++-influx in the amount of autophosphorylated CaM-kinase. This activity can then be expressed for some period of time after the Ca++ concentrations have returned to resting levels. Ca++ plays an important role in many forms of short and long-term neuronal plasticity, which are believed to be the cellular basis for learning and memory. The applicant has been studying the role of Ca++-activated protein kinases (e.g., CaM-kinase) in the hippocampal slice model of cellular learning called long-term potentiation (LTP). Initial experiments have shown that CaM-kinase plays some, as yet unknown, role in the induction process of LTP.