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
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.
引用
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页码:181 / 186
页数:6
相关论文
共 55 条
[51]   MULTIPLE TYPES OF NEURONAL CALCIUM CHANNELS AND THEIR SELECTIVE MODULATION [J].
TSIEN, RW ;
LIPSCOMBE, D ;
MADISON, DV ;
BLEY, KR ;
FOX, AP .
TRENDS IN NEUROSCIENCES, 1988, 11 (10) :431-438
[52]   R-24-571 - A POTENT INHIBITOR OF CALMODULIN-ACTIVATED ENZYMES [J].
VANBELLE, H .
CELL CALCIUM, 1981, 2 (05) :483-494
[53]   CLUSTERING OF L-TYPE CA-2+ CHANNELS AT THE BASE OF MAJOR DENDRITES IN HIPPOCAMPAL PYRAMIDAL NEURONS [J].
WESTENBROEK, RE ;
AHLIJANIAN, MK ;
CATTERALL, WA .
NATURE, 1990, 347 (6290) :281-284
[54]   DIFFERENTIAL EXPRESSION OF IMMEDIATE EARLY GENES IN THE HIPPOCAMPUS AND SPINAL-CORD [J].
WISDEN, W ;
ERRINGTON, ML ;
WILLIAMS, S ;
DUNNETT, SB ;
WATERS, C ;
HITCHCOCK, D ;
EVAN, G ;
BLISS, TVP ;
HUNT, SP .
NEURON, 1990, 4 (04) :603-614
[55]   CONTROL OF POSTSYNAPTIC CA2+ INFLUX IN DEVELOPING NEOCORTEX BY EXCITATORY AND INHIBITORY NEUROTRANSMITTERS [J].
YUSTE, R ;
KATZ, LC .
NEURON, 1991, 6 (03) :333-344