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Targeting inhibition of GluR1 Ser845 phosphorylation with an RNA aptamer that blocks AMPA receptor trafficking.

Publication ,  Journal Article
Liu, Y; Sun, Q-A; Chen, Q; Lee, TH; Huang, Y; Wetsel, WC; Michelotti, GA; Sullenger, BA; Zhang, X
Published in: J Neurochem
January 2009

Phosphorylation at glutamate receptor subunit 1(GluR1) Ser845 residue has been widely accepted to involve in GluR1-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking, but the in vivo evidence has not yet been established. One of the main obstacles is the lack of effective methodologies to selectively target phosphorylation at single amino acid residue. In this study, the Escherichia coli-expressed glutathione-S-transferase-tagged intracellular carboxyl-terminal domain of GluR1 (cGluR1) was phosphorylated by protein kinase A for in vitro selection. We have successfully selected aptamers which effectively bind to phospho-Ser845 cGluR1 protein, but without binding to phospho-Ser831 cGluR1 protein. Moreover, pre-binding of the unphospho-cGluR1 protein with these aptamers inhibits protein kinase A-mediated phosphorylation at Ser845 residue. In contrast, the pre-binding of aptamer A2 has no effect on protein kinase C-mediated phosphorylation at Ser831 residue. Importantly, the representative aptamer A2 can effectively bind the mammalian GluR1 that inhibited GluR1/GluR1-containing AMPA receptor trafficking to the cell surface and abrogated forskolin-stimulated phosphorylation at GluR1 Ser845 in both green fluorescent protein-GluR1-transfected human embryonic kidney cells and cultured rat cortical neurons. The strategy to use aptamer to modify single-residue phosphorylation is expected to facilitate evaluation of the potential role of AMPA receptors in various forms of synaptic plasticity including that underlying psychostimulant abuse.

Duke Scholars

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Published In

J Neurochem

DOI

EISSN

1471-4159

Publication Date

January 2009

Volume

108

Issue

1

Start / End Page

147 / 157

Location

England

Related Subject Headings

  • Transfection
  • Serine
  • Receptors, AMPA
  • Rats
  • Protein Transport
  • Protein Kinase C
  • Protein Binding
  • Phosphorylation
  • Neurons
  • Neurology & Neurosurgery
 

Citation

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Liu, Y., Sun, Q.-A., Chen, Q., Lee, T. H., Huang, Y., Wetsel, W. C., … Zhang, X. (2009). Targeting inhibition of GluR1 Ser845 phosphorylation with an RNA aptamer that blocks AMPA receptor trafficking. J Neurochem, 108(1), 147–157. https://doi.org/10.1111/j.1471-4159.2008.05748.x
Liu, Yingmiao, Qi-An Sun, Qiang Chen, Tong H. Lee, Yangzhong Huang, William C. Wetsel, Gregory A. Michelotti, Bruce A. Sullenger, and Xiuwu Zhang. “Targeting inhibition of GluR1 Ser845 phosphorylation with an RNA aptamer that blocks AMPA receptor trafficking.J Neurochem 108, no. 1 (January 2009): 147–57. https://doi.org/10.1111/j.1471-4159.2008.05748.x.
Liu Y, Sun Q-A, Chen Q, Lee TH, Huang Y, Wetsel WC, et al. Targeting inhibition of GluR1 Ser845 phosphorylation with an RNA aptamer that blocks AMPA receptor trafficking. J Neurochem. 2009 Jan;108(1):147–57.
Liu, Yingmiao, et al. “Targeting inhibition of GluR1 Ser845 phosphorylation with an RNA aptamer that blocks AMPA receptor trafficking.J Neurochem, vol. 108, no. 1, Jan. 2009, pp. 147–57. Pubmed, doi:10.1111/j.1471-4159.2008.05748.x.
Liu Y, Sun Q-A, Chen Q, Lee TH, Huang Y, Wetsel WC, Michelotti GA, Sullenger BA, Zhang X. Targeting inhibition of GluR1 Ser845 phosphorylation with an RNA aptamer that blocks AMPA receptor trafficking. J Neurochem. 2009 Jan;108(1):147–157.
Journal cover image

Published In

J Neurochem

DOI

EISSN

1471-4159

Publication Date

January 2009

Volume

108

Issue

1

Start / End Page

147 / 157

Location

England

Related Subject Headings

  • Transfection
  • Serine
  • Receptors, AMPA
  • Rats
  • Protein Transport
  • Protein Kinase C
  • Protein Binding
  • Phosphorylation
  • Neurons
  • Neurology & Neurosurgery