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REGULATION OF GENE-EXPRESSION IN HIPPOCAMPAL-NEURONS BY DISTINCT CALCIUM SIGNALING PATHWAYS
被引:1000
作者:
BADING, H
[1
]
GINTY, DD
[1
]
GREENBERG, ME
[1
]
机构:
[1] HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,200 LONGWOOD AVE,BOSTON,MA 02115
来源:
关键词:
D O I:
10.1126/science.8097060
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
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.
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页码:181 / 186
页数:6
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