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Previous Article | Next Article
The Journal of Neuroscience, August 1, 2001, 21(15):5484-5493
Arg3.1/Arc mRNA Induction by Ca2+ and cAMP Requires Protein Kinase A and Mitogen-Activated Protein Kinase/Extracellular Regulated Kinase Activation
Robert Waltereit1, Björn Dammermann1, Peer Wulff1, Joey Scafidi2, Ursula Staubli2, Gunther Kauselmann1, Marsha Bundman1, and Dietmar Kuhl1 1 Institut fuer Neurale Signalverarbeitung, Zentrum für Molekulare Neurobiologie Hamburg, 20246 Hamburg, Germany, and 2 Center for Neural Science, New York University, New York, New York 10003
Long-term potentiation (LTP) is a cellular model for persistent synaptic plasticity in the mammalian brain. Like several forms of memory, long-lasting LTP requires cAMP-mediated activation of protein kinase A (PKA) and is dependent on gene transcription. Consequently, activity-dependent genes such as c-fos that contain cAMP response elements (CREs) in their 5' regulatory region have been studied intensely. More recently, arg3.1/arc became of interest, because after synaptic stimulation, arg3.1/arc mRNA is rapidly induced and distributed to dendritic processes and may be locally translated there to facilitate synapse-specific modifications. However, to date nothing is known about the signaling mechanisms involved in the induction of this gene. Here we report that arg3.1/arc is robustly induced with LTP stimulation even at intensities that are not sufficient to activate c-fos expression. Unlike c-fos, the 5' regulatory region of arg3.1/arc does not contain a CRE consensus sequence and arg3.1/arc is unresponsive to cAMP in NIH3T3 and Neuro2a cells. However, in PC12 cells and primary cultures of hippocampal neurons, arg3.1/arc can be induced by cAMP and calcium. This induction requires the activity of PKA and mitogen-activated protein kinase, suggesting a neuron-specific pathway for the activation of arg3.1/arc expression.
Key words: plasticity; long-term memory; hippocampus; LTP; gene induction; Arg3.1; Arc
Copyright © 2001 Society for Neuroscience 0270-6474/01/21155484-10$05.00/0
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