REGULATION OF GENE-EXPRESSION IN HIPPOCAMPAL-NEURONS BY DISTINCT CALCIUM SIGNALING PATHWAYS
REGULATION OF GENE-EXPRESSION IN HIPPOCAMPAL-NEURONS BY DISTINCT CALCIUM SIGNALING PATHWAYS
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DOI：
10.1126/science.8097060
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发表时间：
1993-04-09
期刊：
影响因子：
56.9
通讯作者：
GREENBERG, ME
中科院分区：
文献类型：
--
作者：
BADING, H;GINTY, DD;GREENBERG, ME
钙离子(Ca~(2+))作为细胞内的第二信使，通过多种离子通道进入神经元。钙离子通过不同类型的钙离子通道的内流可能会不同地激活生化过程。N-甲基-D-天冬氨酸受体和L钙通道是钙离子进入海马神经元的两个主要部位，它们通过两条不同的钙信号通路将信号传递到海马神经元并调节基因转录。N-甲基-D-天冬氨酸受体或L型钙通道均可激活多功能钙调素依赖性蛋白激酶(CaM-K)，但CaM-K的激活似乎仅在将L-型钙通道信号传递到细胞核中起关键作用。此外，NMDA型受体和L钙通道通路通过c-fos启动子中不同的顺式调控元件激活转录。这些结果表明，钙离子可以激活两条不同的信号通路，这取决于它进入神经元的方式。差异信号处理可能提供了一种机制，通过这种机制，钙离子可以控制不同的细胞功能。
Calcium ions (Ca2+) act as an intracellular second messenger and can enter neurons through various ion channels. Influx of Ca2+ through distinct types of Ca2+ channels may differentially activate biochemical processes. N-Methyl-D-aspartate (NMDA) receptors and L-type Ca2+ channels, two major sites of Ca2+ entry into hippocampal neurons, were found to transmit signals to the nucleus and regulated gene transcription through two distinct Ca2+ signaling pathways. Activation of the multifunctional Ca2+-calmodulin-dependent protein kinase (CaM kinase) was evoked by stimulation of either NMDA receptors or L-type Ca2+ channels; however, activation of CaM kinase appeared to be critical only for propagating the L-type Ca2+ channel signal to the nucleus. Also, the NMDA receptor and L-type Ca2+ channel pathways activated transcription by means of different cis-acting regulatory elements in the c-fos promoter. These results indicate that Ca2+, depending on its mode of entry into neurons, can activate two distinct signaling pathways. Differential signal processing may provide a mechanism by which Ca2+ controls diverse cellular functions.