RT Journal Article
SR Electronic
T1 Regulation of gene expression in hippocampal neurons by distinct calcium signaling pathways
JF Science
JO Science
FD American Association for the Advancement of Science
SP 181
OP 186
DO 10.1126/science.8097060
VO 260
IS 5105
A1 Bading, H
A1 Ginty, DD
A1 Greenberg, ME
YR 1993
UL http://science.sciencemag.org/content/260/5105/181.abstract
AB 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.