Arc/Arg3.1 translation is controlled by convergent N-methyl-D-aspartate and Gs-coupled receptor signaling pathways.

Loading...
Thumbnail Image

Date

2008-01

Journal Title

Journal ISSN

Volume Title

Citation Stats

Abstract

Arc/Arg3.1 is an immediate early gene whose expression is necessary for the late-phase of long-term potentiation (LTP) and memory consolidation. Whereas pathways regulating Arc transcription have been extensively investigated, less is known about the role of post-transcriptional mechanisms in Arc expression. Fluorescence microscopy experiments in cultured hippocampal neurons revealed that Arc protein level was dramatically increased by activation of the cAMP-dependent protein kinase (PKA) pathway, which is implicated in long-term memory. A PKA-dependent increase in Arc protein level was observed after pharmacological or synaptic activation of N-methyl-D-aspartate (NMDA) receptors, which play a critical role in both LTP induction and learning. Arc protein was also up-regulated by activation of PKA through G(s)-coupled dopamine and beta-adrenergic receptors, which regulate the late-phase of LTP and memory. When agonists for the NMDA and G(s)-coupled receptors were co-applied, they had an additive effect on Arc protein expression. Interestingly, G(s)-coupled receptor stimulation was ineffective in the presence of an NMDA receptor antagonist, suggesting calcium influx through the NMDA receptor plays a gating role in this pathway. Stimulation of the cAMP/PKA pathway did not affect Arc mRNA level or protein stability, identifying translational efficacy as the main determinant of Arc protein expression level. It is concluded that efficient Arc translation requires NMDA receptor activity, whereas a further enhancement can be achieved with activation of G(s)-coupled receptors. These experiments have, therefore, revealed remarkable similarities in the signaling pathways that control Arc expression and those that regulate LTP, learning, and memory.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1074/jbc.m702451200

Publication Info

Bloomer, Wendy AC, Hendrika MA VanDongen and Antonius MJ VanDongen (2008). Arc/Arg3.1 translation is controlled by convergent N-methyl-D-aspartate and Gs-coupled receptor signaling pathways. The Journal of biological chemistry, 283(1). pp. 582–592. 10.1074/jbc.m702451200 Retrieved from https://hdl.handle.net/10161/30437.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

VanDongen

Antonius M. J. VanDongen

Associate Professor of Pharmacology & Cancer Biology

We have discovered a new connection between the memory gene Arc (Activity Regulated, Cytoskeletal-associated protein) and Alzheimer's disease. Arc is a master regulator of of synaptic plasticity and epigenetically controls the transcription of 1900 genes associated with with synaptic function, neuronal plasticity, intrinsic excitability (channels, receptors, transporters), and signaling pathways (transcription factors/regulators). Approximately 100 genes whose activity-dependent expression level depends on Arc are associated with the pathophysiology of Alzheimer’s disease, suggesting a critical role for Arc in the development of neurodegenerative disorders.


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.