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(Sackler NAS Colloquium) Neural Signaling (2002)
National Academy of Sciences (NAS)

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Neural Signaling: Arthur M. Sackler Colloquia of the National Academy of Sciences

the ability of these channels to promote gene expression. Next, we have demonstrated that different stimuli drive phosphorylation of the transcription factor CREB at unique sites, altering its transcriptional activity. Finally, we have seen that the neuron- and calcium-specific induction of BDNF promoter III is mediated in part by the coordinated action of three separate transcription factors, each of which seems to be activated by a distinct but overlapping set of intracellular signaling pathways. The challenge for the future is to link these steps together and to understand the molecular mechanisms that regulate them. For example, if calcium influx through L-VSCCs leads to specific sites of phosphorylation on CREB, is this the result of local tethering of signaling molecules to the L-VSCCs that then mediate these phosphorylation events? Could calcium-specific phosphorylation of CREB play a role in calcium-specific induction of BDNF promoter III? If so, how does altered CREB phosphorylation regulate its ability to interact with the other two transcription factors at the promoter? These and other similar questions will drive future efforts to obtain a more detailed understanding of long-term activity-dependent plasticity and gene expression in the brain.

M.E.G. acknowledges the generous support of the F.M.Kirby Foundation to the Division of Neuroscience. This work was supported by a Mental Retardation Research Center Grant (HD18655) and a National Institutes of Health Grant (NS28829–07) (to M.E.G.), an American Cancer Society Postdoctoral Fellowship (to A.E.W.), a Howard Hughes Medical Institute Predoctoral Fellowship (to W.G.C.), and by a Helen Hay Whitney Foundation Postdoctoral Fellowship (to R.E.D.). M.B.D. is a Chiron Life Science Research Foundation Fellow.

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