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Molecular and Cellular Biological Study on the Actions of Intracellular Calcium Ion in Cultured Cells

培养细胞内钙离子作用的分子和细胞生物学研究

基本信息

批准号：
05454668
负责人：
MIYAMOTO Eishichi
金额：
$ 4.22万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454668/
关键词：
Calcium mobilization CaM kinase II Neuron Glia Enzyme activation Glutamate receptor Long-term potentiation Culturesd cell プロテインホスファターゼ蛋白質燐酸化反応

项目摘要

Nerve impulses, various neurotransmitters, and growth hormones exert their effects through elevation of the intracellular concentration of calcium ion (Ca^<2+>). Ca^<2+> is involved in several types of neuronal functions including biosynthesis of neurotransmitters, stimulus-secretion coupling of neurotransmitters and hormones, microtubule assembly-diassembly cycle, synaptic plasticity, gene expression and many metabolic reactions. These include the short-term and long-term events with respect to time course. Although the precise molecular mechanisms mediating the actions of Ca^<2+> in the brain diverse, accumulating evidence suggests the effects of Ca^<2+> are mediated through Ca^<2+>-binding proteins. Furthermore, many of the functions are ultimately conducted by protein kinases and protein phosphatases in a Ca^<2+>-dependent manner. In an attempt to elucidate the functions in the central nervous system through calcium signaling pathways, we have been examining the dynamic state of activation of Ca^<2+>/calmodulin-dependent protein kinase II (CaM kinase II) in primary cultures of neurons and glias and established cell systems. We found that CaM kinase II is activated through elevation of intracellular Ca^<2+> in response to the extracellular stimuli. Firthermore, with concomitant activation of the enzyme, phosphorylation of endogenous substrates, activation of the enzyme and long-term potentiation were observed.

神经冲动、各种神经递质和生长激素通过升高细胞内钙离子（Ca^<2+>）浓度发挥作用。Ca^<2+>参与多种类型的神经元功能，包括神经递质的生物合成、神经递质和激素的刺激-分泌偶联、微管组装-解聚周期、突触可塑性、基因表达和许多代谢反应。这些包括与时间进程有关的短期和长期事件。虽然调节Ca^<2+>在大脑中作用的精确分子机制多种多样，但越来越多的证据表明Ca^<2+>的作用是通过Ca^<2+>结合蛋白介导的。此外，许多功能最终由蛋白激酶和蛋白磷酸酶以Ca^2+依赖性方式进行。为了阐明钙信号通路在中枢神经系统中的功能，我们一直在研究原代培养的神经元和胶质细胞以及已建立的细胞系统中Ca^2+/钙调蛋白依赖性蛋白激酶II（CaM激酶II）的激活动态。我们发现，CaM激酶II是通过细胞内Ca^2+的升高而被激活的，这是对细胞外刺激的反应。首先，伴随着酶的激活，内源性底物的磷酸化，酶的激活和长时程增强被观察到。