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Science 9 April 1993: Vol. 260. no. 5105, pp. 181 - 186 DOI: 10.1126/science.8097060
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Articles
Science, Vol 260, Issue 5105, 181-186
Copyright © 1993 by American Association for the Advancement of Science
Regulation of gene expression in hippocampal neurons by distinct calcium signaling pathways
H Bading,
DD Ginty,
and
ME Greenberg
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115.
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 Ca(2+)-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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- Rocker Is a New Variant of the Voltage-Dependent Calcium Channel Gene Cacna1a.
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- D2 Dopamine Receptors in Striatal Medium Spiny Neurons Reduce L-Type Ca2+ Currents and Excitability via a Novel PLC{beta}1-IP3-Calcineurin-Signaling Cascade.
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- Repression of Activity-Dependent c-fos and Brain-Derived Neurotrophic Factor mRNA Expression by Pyrethroid Insecticides Accompanying a Decrease in Ca2+ Influx into Neurons.
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