Abstract
Although it has been established that an activity-dependent gene transcription is induced by the calcium (Ca(2+)) signals in neurons, it is unclear how the specific mRNA moieties are transiently accumulated in response to synaptic transmission which evokes multiple intracellular signals including Ca(2+) and cAMP ones. The expression of pituitary adenylate cyclase activating polypeptide (PACAP), a neuropeptide, is controlled by Ca(2+) signals evoked via membrane depolarization in neurons, and, in cultured rat cortical neuronal cells, we found that the Ca(2+) signal-mediated activation of the PACAP gene promoter was critically controlled by a single cAMP-response element (CRE) located at around -200, to which the CRE-binding protein predominantly bound. The Ca(2+) signal-induced expression of PACAP mRNA was enhanced by forskolin, which evokes cAMP signals. In support, the PACAP gene promoter was synergistically enhanced by Ca(2+) and cAMP signals through the CRE, accompanying a prolonged activation of extracellular signal-related protein kinase 1/2 and CRE-binding protein. On the other hand, sole administration of forskolin markedly reduced the cellular content of PACAP mRNA, which was restored by the addition of Ca(2+) signals. ...Continue Reading
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