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

Publication ,  Journal Article
Bloomer, WAC; VanDongen, HMA; VanDongen, AMJ
Published in: J Biol Chem
January 4, 2008

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.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

January 4, 2008

Volume

283

Issue

1

Start / End Page

582 / 592

Location

United States

Related Subject Headings

  • Transfection
  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Recombinant Fusion Proteins
  • Receptors, N-Methyl-D-Aspartate
  • Rats
  • Protein Biosynthesis
  • Nerve Tissue Proteins
  • N-Methylaspartate
  • Microscopy, Fluorescence
 

Citation

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Bloomer, W. A. C., VanDongen, H. M. A., & VanDongen, A. M. J. (2008). Arc/Arg3.1 translation is controlled by convergent N-methyl-D-aspartate and Gs-coupled receptor signaling pathways. J Biol Chem, 283(1), 582–592. https://doi.org/10.1074/jbc.M702451200
Bloomer, Wendy A. C., Hendrika M. A. VanDongen, and Antonius M. J. VanDongen. “Arc/Arg3.1 translation is controlled by convergent N-methyl-D-aspartate and Gs-coupled receptor signaling pathways.J Biol Chem 283, no. 1 (January 4, 2008): 582–92. https://doi.org/10.1074/jbc.M702451200.
Bloomer WAC, VanDongen HMA, VanDongen AMJ. Arc/Arg3.1 translation is controlled by convergent N-methyl-D-aspartate and Gs-coupled receptor signaling pathways. J Biol Chem. 2008 Jan 4;283(1):582–92.
Bloomer, Wendy A. C., et al. “Arc/Arg3.1 translation is controlled by convergent N-methyl-D-aspartate and Gs-coupled receptor signaling pathways.J Biol Chem, vol. 283, no. 1, Jan. 2008, pp. 582–92. Pubmed, doi:10.1074/jbc.M702451200.
Bloomer WAC, VanDongen HMA, VanDongen AMJ. Arc/Arg3.1 translation is controlled by convergent N-methyl-D-aspartate and Gs-coupled receptor signaling pathways. J Biol Chem. 2008 Jan 4;283(1):582–592.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

January 4, 2008

Volume

283

Issue

1

Start / End Page

582 / 592

Location

United States

Related Subject Headings

  • Transfection
  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Recombinant Fusion Proteins
  • Receptors, N-Methyl-D-Aspartate
  • Rats
  • Protein Biosynthesis
  • Nerve Tissue Proteins
  • N-Methylaspartate
  • Microscopy, Fluorescence