PKA-mediated phosphorylation of Dexras1 suppresses iron trafficking by inhibiting S-nitrosylation

Yong Chen, Lauren Mathias, Juliana M. Falero-Perez, Sangwon Kim

Research output: Contribution to journalArticle

Abstract

Dexras1 is a small GTPase and plays a central role in neuronal iron trafficking. We have shown that stimulation of glutamate receptors activates neuronal nitric oxide synthase, leading to S-nitrosylation of Dexras1 and a physiological increase in iron uptake. Here we report that Dexras1 is phosphorylated by protein kinase A (PKA) on serine 253, leading to a suppression of iron influx. These effects were directly associated with the levels of S-nitrosylated Dexras1, whereby PKA activation reduced Dexras1 S-nitrosylation in a dose dependent manner. Moreover, we found that adiponectin modulates Dexras1 via PKA. Hence these findings suggest the involvement of the PKA pathway in modulating glutamate-mediated ROS in neurons, and hint to a functional crosstalk between S-nitrosylation and phosphorylation.

Original languageEnglish (US)
Article number37351
Pages (from-to)3212-3219
Number of pages8
JournalFEBS Letters
Volume589
Issue number20
DOIs
StatePublished - Oct 7 2015
Externally publishedYes

Fingerprint

Phosphorylation
Cyclic AMP-Dependent Protein Kinases
Iron
Nitric Oxide Synthase Type I
Monomeric GTP-Binding Proteins
Adiponectin
Glutamate Receptors
Crosstalk
Serine
Neurons
Glutamic Acid
Chemical activation

Keywords

  • Iron
  • Neuron
  • Nitric oxide
  • Phosphorylation
  • Post-translational modification
  • S-nitrosylation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

Cite this

PKA-mediated phosphorylation of Dexras1 suppresses iron trafficking by inhibiting S-nitrosylation. / Chen, Yong; Mathias, Lauren; Falero-Perez, Juliana M.; Kim, Sangwon.

In: FEBS Letters, Vol. 589, No. 20, 37351, 07.10.2015, p. 3212-3219.

Research output: Contribution to journalArticle

Chen, Yong ; Mathias, Lauren ; Falero-Perez, Juliana M. ; Kim, Sangwon. / PKA-mediated phosphorylation of Dexras1 suppresses iron trafficking by inhibiting S-nitrosylation. In: FEBS Letters. 2015 ; Vol. 589, No. 20. pp. 3212-3219.
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